nit 2 - Energy Metabolism

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Introduction to Unit 2  

Welcome to Unit 2!  In this unit, you will learn about exercise metabolism. Exercise metabolism refers to how the body provides the energy that is necessary to do the work of exercise. Unit 2 is divided into four lessons with 10 major topics in these lessons. A complete outline of the Unit topics is given later in this lesson. In addition, there are two labs associated with this unit: Lab 2 represents the technical aspects of measuring oxygen consumption, and Lab 3 represents the response of oxygen consumption to exercise.

Assignments

1.  Read, study and master the content presented online in Lessons 1-4 and in Labs 2 and 3. You can access the labs any time you want and you may want to start  the labs before finishing the lessons. But I encourage you to complete at least Lesson 2 before doing Lab 2, and to complete at least Lesson 3 before doing Lab 3. You do not have to do the labs until you have completed all four lessons in the unit.

2.  Read and study in the textbook:

  • Chapter 3, "Bioenergetics"
  • Chapter 4, "Exercise Metabolism"

You may also want to check key terms in the textbook index; sometimes topics are addressed in several places throughout a textbook.

3.  Participate in conference discussions on WebBoard.

4.  Check the course Announcements Page for other possible assignments.

 

 

 
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Outline of Unit Content

Following is an outline of the content of Unit 2 - Metabolism. The pertinent sections of this outline are also listed at the beginning of each lesson. The purpose of the outline here is to show how the topics of the entire unit are organized.

Outline:

I.  Definitions of energy metabolism, catabolism
          and anabolism
(Lesson 1)

II.  ATP – General considerations (Lesson 1)

   A.  Description

   B.  ATP hydrolysis

   C.  Formation of ATP

      1.  CK Reaction

         a.  Description
         b.  Advantages and disadvantages (limitations)

      2.  Anaerobic glycolysis

         a.  Description
         b.  Advantages and disadvantages (limitations)

      3. Aerobic (oxidative) metabolism

         a.  General description
         b.  Aerobic catabolism of carbohydrates
         c.  Aerobic catabolism of fats
         d.  Aerobic catabolism of proteins
        
e.  Aerobic metabolism – summary
         f.  Advantages and disadvantages (limitations) of
            aerobic metabolism

   D. Formation of ATP – Summary

III.  Formation of ATP during exercise (Lesson 2)

   A.  Principles

   B.  Application of principles – Analysis of specific activities

      1.  Running a marathon in 3 hours
      2.  Running 100 meters in 12.00 seconds

   C.  Summary – Potential metabolic limitations of exercise

IV.  Carbohydrates, fats and proteins as substrates for aerobic metabolism (Lesson 2)

   A.  Carbohydrates and fats – Contrasts; advantages and limitations

   B.  Effect of exercise intensity on proportions of carbohydrates and fats used

   C.  Effect of exercise duration on proportions of carbohydrates and fats used

   D.  Protein use

   E.  Effect of diet

V.  Lactic Acid Metabolism (Lesson 3)

   A.  Introduction

   B.  Fates of lactic acid

   C.  Response of blood lactic acid concentration to exercise

      1.  Introduction
      2.  Lactate threshold (OBLA—Onset of Blood Lactate
          Accumulation)
     
3.  Maximal lactate steady state

VI.  Maintenance of Blood Glucose (Lesson 3)

VII.  Recovery From Exercise (Lesson 3)

VIII.  Effect of Training on Energy Metabolism (Lesson 4)

IX.  Regulation of energy metabolism (Lesson 4)

X.  Aerobic and anaerobic terminology (Lesson 4)

Lab 2 - Measurement of Oxygen Consumption

Lab 3 - Oxygen Consumption in Response to Acute Exercise

 

 
 
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Lesson 1

Lesson 1 presents information that is basic to energy metabolism in general. This is the essential foundation for the specific study of exercise metabolism in the lessons that follow.

Learning Objectives

After completion of Lesson 1, the student should be able to:

1. Define the following terms, and be able to use each term appropriately in discussions: energy metabolism, catabolism, anabolism, ATP, ADP, ATP hydrolysis, ADP phosphorylation, CK, CP, anaerobic glycolysis, aerobic glycolysis, lactic acid, aerobic metabolism, electron transport system, Krebs Cycle, glycogen, fatty acid, triglyceride, lipoprotein, amino acid.

2. Discuss the critical role of ATP hydrolysis and ADP phosphorylation in exercise physiology.

3. List the three methods or systems the body has for making ATP, and the strengths and weaknesses of each method.

4. Discuss the role of NAD and FAD in energy metabolism.

5. Discuss the relationships among the following: aerobic glycolysis, Krebs Cycle, beta oxidation, electron transport system.  

Outline of Content

I.  Definitions of energy metabolism, catabolism and anabolism

II.  ATP – General considerations

   A.  Description

   B.  ATP hydrolysis

   C.  Formation of ATP

      1.  CK Reaction

         a.  Description
         b.  Advantages and disadvantages (limitations)

      2.  Anaerobic glycolysis

         a.  Description
         b.  Advantages and disadvantages (limitations)

      3. Aerobic (oxidative) metabolism

         a.  General description
         b.  Aerobic catabolism of carbohydrates
         c.  Aerobic catabolism of fats
         d.  Aerobic catabolism of proteins
        
e.  Aerobic metabolism – summary
         f.  Advantages and disadvantages (limitations)
             of aerobic metabolism

   D. Formation of ATP – Summary 

 

 

 

 
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Definitions of Energy Metabolism, Catabolism and Anabolism

Energy metabolism may be defined as “the chemical reactions in the body that are involved in changing energy from one form to another or in transferring energy from one chemical substance to another.” There are two sides to the energy metabolism coin: catabolism and anabolism.

Catabolism includes the chemical reactions in which larger molecules are broken down to smaller ones, and anabolism includes the reactions in which larger molecules are formed from smaller molecules.

In catabolic reactions, chemical energy is made available as the larger, higher energy molecules are broken down. In anabolic reactions, energy must be added so the smaller, lower energy molecules can form the higher energy larger molecules.

 
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Definitions of Energy Metabolism, Catabolism and Anabolism (cont.)

Let me briefly present two examples.

Example 1: Proteins, such as the contractile proteins of skeletal muscle, myosin and actin, consist of many amino acids attached to each other by so-called peptide bonds. When proteins are broken down to the individual amino acids (such as in digestion of dietary protein, or in muscle atrophy due to lack of exercise or muscle wasting diseases), this is catabolism. In this process, energy that had been stored in the protein molecules is liberated. In contrast, when skeletal muscles are being built up (such as during normal growth in childhood, or the hypertrophy that occurs with weight training), this is anabolism. Individual amino acids are bonded together in specific sequences to form the proteins. Formation of these bonds requires energy that must come from other chemical reactions.

Example 2: Carbohydrates are stored in the body primarily in the form of glycogen. Glycogen is nothing more than many glucose molecules attached end to end (with branching). The breakdown of glycogen to glucose is the first step in deriving the energy from glycogen. Ultimately energy is derived from glucose as it is broken down to smaller substances, such as carbon dioxide and water. Glucose can be formed from smaller substances, although human tissues cannot make glucose from carbon dioxide and water. (Plants do this in photosynthesis, transforming energy from the sun into chemical energy stored in glucose.) Human tissues can make glucose from other smaller molecules, such as lactic acid and pyruvic acid (we will study this more later). And when they do, energy must be added to the molecule. Even the process of adding glucose molecules to each other to form glycogen requires activation of each glucose molecule, and this requires energy.

 

 
 
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Definitions of Energy Metabolism, Catabolism and Anabolism (cont.)

As a general principle, catabolic and anabolic reactions are coupled together. This means that the energy liberated as certain higher energy large molecules are broken down to smaller ones is used to form other larger molecules from smaller ones. Of course, the body is not perfectly efficient in such energy transfers, and much of the chemical energy liberated in catabolism is transformed to heat.

 
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ATP – General Considerations

An extremely important chemical substance in energy metabolism is ATP (the full name is adenosine triphosphate). If any cell in the body runs out of ATP, the cell’s functions cease and the cell quickly dies unless the ATP is replenished. ATP is made up of a substance known as adenosine that has three individual phosphate molecules (hence the term TRIphosphate)attached end to end. This could be abbreviated: A – P – P – P (the dashes represent the chemical bonds that attach one part of the molecule to the other).

Adenosine sometimes has only one phosphate attached (in this form it is called adenosine monophosphate, or AMP), and sometimes two phosphates (adenosine diphosphate, ADP). But when adenosine has three phosphates attached (ATP), it exists in its highest energy form.

In fact, ATP is often referred to as a “high-energy phosphate compound,” and the bond that joins the third phosphate to the second on ATP is often called a “high energy phosphate bond.” When this bond is broken so that the third phosphate is broken off, a lot of chemical energy is liberated. Conversely, to form this bond (i.e., to add the third phosphate), a lot of energy must be added.

The breakdown of ATP is called ATP hydrolysis, and this chemical reaction may be summarized as follows:

     ATP ==> ADP + P + Energy

The speed of this reaction is controlled by the enzyme ATPase.

 

 
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ATP – General Considerations (cont.)

Most formation of ATP involves phosphorylation of ADP, that is, attaching a single phosphate (technically known as inorganic phosphate) to ADP. 

The figure below summarizes ATP hydrolysis and ADP phosphorylation.

What makes ATP so important?

Most chemical reactions in the body that require energy to make the reactions take place get that energy directly from ATP hydrolysis. Most importantly in exercise physiology, the development of force by a muscle in contraction absolutely requires energy from ATP hydrolysis. This energy for muscle contraction cannot come from any other source.

 

 
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ATP – General Considerations (cont.)

Given this absolute dependence on ATP for muscle contraction, there are some apparent paradoxes in skeletal muscle.

First, there is very little ATP stored in a muscle fiber; if muscle had to rely only on its stored ATP, there would be enough to supply the energy for only 2-3 seconds of vigorous contractions. 

Second, after a muscle fiber has been contracting vigorously and is fatigued (i.e., can’t continue to develop force at the same rate), the ATP in the fiber is not totally depleted. In fact, the ATP concentration may be reduced by only 50% or so.

In other words, during vigorous and continued contraction, ATP is hydrolyzed at a very high rate (to provide the energy for force development), but the ATP is not completely depleted, even though there was not much in the muscle fibers before they started to contract. How can this riddle be explained? The answer is that muscle fibers normally have very effective mechanisms for replenishing the ATP as it is being used. Understanding the mechanisms by which muscle fibers replenish ATP during contraction is fundamental.

 

 
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Formation of ATP

Muscle fibers have three systems or methods for making ATP:

(a) the CK (creatine kinase) reaction,

(b) anaerobic glycolysis, and

(c) aerobic (oxidative) metabolism.

Each of these methods has advantages over the other methods, but each also has disadvantages or limitations. By having all three methods, the total replenishment system is extremely effective over a very wide range of muscular activities from the 40-yard dash that demands very high power but little endurance, to the marathon run that demands great endurance but only moderate power.

On the following pages is a summary of each of the three methods of forming ATP, and a summary of the advantages and limitations of each.

 

 
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Formation of ATP – The CK Reaction

The CK reaction is a single chemical reaction in which ADP is phosphorylated by transferring a phosphate from the substance creatine phosphate (CP; sometimes also called phosphocreatine, PC). The resulting products of this reaction are ATP and creatine. CK is the enzyme that controls the rate of this reaction. The reaction may be summarized:

     CP + ADP ==> ATP + C

NOTE: Some exercise physiologists refer to the method of making ATP by the CK reaction as the “CP system,” to emphasize the high-energy compound that is a substrate for the CK reaction, and from which the energy for making ATP comes. I prefer to emphasize the enzyme, CK, that makes the reaction go rapidly. Others (including the authors of the textbook) refer to the “ATP-CP system.” I think this is misleading. It is fundamental to realize that the energy for muscle contraction and many other activities in the body comes directly from ATP hydrolysis, and there is no other option. Then the question is: “How is the ATP replenished?” The CK reaction is one method of replenishment, as are glycolysis and aerobic metabolism.

 

 
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Formation of ATP – The CK Reaction (cont.)

The advantages of forming ATP by the CK reaction are:

(a) The reaction is anaerobic, which means that no oxygen is required. Therefore this reaction is not dependent on the cardiorespiratory system or the so-called oxygen transport system.

(b) This method can form ATP at the highest rate of all the methods (i.e., it has the highest rate of energy transfer or power).

(c) The rate of response of the CK reaction to a need for ATP is very rapid. In fact, the CK reaction can instantaneously form ATP at its maximal rate when needed. In other words, essentially the instant an ATP is hydrolyzed to form ADP, the ADP can be phosphorylated back to ATP by the CK reaction. 

The important limitation of the CK reaction is its low capacity for total amount of energy transferred (i.e., ATP formed). This is determined by the amount of CP in the active skeletal muscle fibers. A fiber normally has enough CP to form ATP for only about 10-15 seconds of vigorous contraction. CP concentrations close to zero have been measured in fatigued muscle fibers after very high intensity exercise. When the CP is depleted, ATP cannot be formed by this method. When this occurs, the ability of the muscle fibers to generate power is greatly reduced.

 

 
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Formation of ATP – The CK Reaction (cont.)

As a general guideline, if we consider the whole body exercising with large muscle groups (e.g., running, swimming), the maximal power of the CK reaction is about 60 kcal/min or 1 kcal/sec, and the energy capacity of the CK reaction (i.e., the upper limit of energy that can be transferred) is about 10-15 kcal. In other words, when the body needs a lot of muscle tissue to generate ATP as fast as possible, the CK reaction can transfer energy from CP to ADP at the equivalent rate of about 1 kcal/sec. But the muscles have a total equivalent of only 10-15 kcal of CP stored in them. So, the CK reaction could go at the rate of 1 kcal/sec only until 10-15 kcal were turned over, which would be 10-15 seconds.

Note that the numbers presented on this page for the maximal power and the energy capacity of the CK reaction are general guidelines to facilitate understanding of concepts. Actual numbers vary from one person to another and depend on body size (especially total muscle mass), fitness level or training status, and perhaps other variables.

 

 
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Formation of ATP – The CK Reaction (cont.)

To be complete, I want to mention another method by which ATP is formed in muscle fibers through a single chemical reaction, sometimes called the myokinase reaction. This is an important reaction but less important than the CK reaction in terms of amount of ATP formed. For simplicity I am including all ATP formed by either of these single reactions as the product of the CK reaction.

 

 
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Formation of ATP – Anaerobic Glycolysis

Anaerobic glycolysis is a series of about 10 chemical reactions by which a 6-carbon sugar molecule is broken down (catabolized), first to two 3-carbon pyruvic acid molecules and then to two 3-carbon molecules of lactic acid. In certain reactions in this series, ATP is actually used, and in other reactions ATP is formed. When ATP is formed, energy originally stored in the sugar molecule is transferred to the ATP molecule. The net result is formation of two or three ATPs for each glucose converted to lactic acid.

The most common sugar that is the initial substrate for glycolysis is glucose. This glucose can come from the blood, or in muscle fibers it can also come from glycogen stored in the fibers. Glycogen is a large molecule made up of many glucose molecules, and it is a way to store glucose for later use. Muscle fibers can use other sugars (e.g., fructose) as substrate for glycolysis, but normally the major substrate by far is glucose. A very important point to note is that glycolysis (which literally means “breakdown of glucose”) can only use carbohydrates as substrate. Fats and proteins cannot be catabolized via glycolysis.

 

 
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Formation of ATP – Anaerobic Glycolysis (cont.)

The advantages of forming ATP by anaerobic glycolysis are:

(a) This is an anaerobic mechanism (as is the CK reaction) and therefore it is not dependent on the oxygen transport system.

(b) The maximal power of glycolysis is high, although not as high as the maximal power of the CK reaction. That is, ATP can be formed very rapidly via glycolysis, faster than via aerobic metabolism, but not as fast as when the CK reaction is operating at its maximum rate.

(c) Anaerobic glycolysis responds rapidly to a need for ATP. This system can increase to its maximal rate of ATP formation perhaps instantaneously, but certainly within 10-15 seconds.

 

 
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Formation of ATP – Anaerobic Glycolysis (cont.)

The limitation of anaerobic glycolysis is that the endproduct, lactic acid, causes the cellular environment to become acidic (a condition known as acidosis). This can affect many things in the muscle fiber, as well as more generally, since the lactic acid will enter the blood and circulate throughout the body. When glycolysis forms ATP at a high rate, lactic acid is formed at a high rate also, and this eventually limits glycolysis itself. The capacity of anaerobic glycolysis for forming ATP is three to four times higher than the capacity of the CK reaction (i.e., about three to four times more ATP can be formed by glycolysis than by the CK reaction), but it is still relatively low compared with aerobic metabolism. 

To give a general guideline, the maximal power of anaerobic glycolysis is about 30 kcal/min or 0.5 kcal/sec, and the energy capacity of anaerobic glycolysis is about 50 kcal for whole body exercising of large muscle groups. This capacity is not limited by amount of initial substrate, as in the CK reaction, but rather by the lactic acidosis that occurs when glycolysis is rapid. So, anaerobic glycolysis could continue to form ATP for only about 100 seconds at its maximal rate (50 kcal / 0.5 kcal/sec).

 

 
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Formation of ATP – Anaerobic Glycolysis (cont.)

I want to make several points about lactic acid. It is true that lactic acid can lead to muscular fatigue due to acidosis (increased acidity). But lactic acid also has important positive features.

First, lactic acid is formed from pyruvic acid in the very last of the series of chemical reactions in anaerobic glycolysis. If this conversion of pyruvic acid to lactic acid did not occur, anaerobic glycolysis would stop much sooner; that is, much less ATP could be formed from anaerobic glycolysis (i.e., the energy capacity of anaerobic glycolysis would be much less than 50 kcal). So the formation of lactic acid is essential for muscle fibers to have anaerobic glycolysis as an optional method for forming ATP.

Second, each lactic acid molecule is essentially half of a glucose molecule, and therefore a lot of energy is still stored in lactic acid. Certain tissues actually use lactic acid as a starting substrate for metabolic reactions, using the energy stored in lactic acid to form ATP in aerobic metabolism. Other tissues convert lactic acid back to glucose. In short, lactic acid is a very important metabolite with many positive aspects. 

We will study more about lactic acid metabolism later.

 

 
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Formation of ATP – Aerobic Metabolism

Aerobic metabolism (also commonly known as oxidative metabolism) involves a long and complex series of chemical reactions by which any of the three main foodstuffs—carbohydrates, fats, and proteins—can be broken down to make energy available for phosphorylation of ADP.  It would take at least a one-semester course of biochemistry to begin to understand the individual chemical reactions and the pathways involved in aerobic metabolism. I will give only a brief overview in this unit.

Most phosphorylation of ADP to form ATP takes place in the electron transport system (ETS; sometimes also called electron transport chain or the respiratory chain), which is located in mitochondria of muscle fibers and other cells. Hydrogen atoms with their associated electrons are brought to the ETS by the compounds known as NADH2 and FADH2. These electrons and hydrogens are then passed along in succession to other compounds, known as cytochromes (remember, the system is called the “electron transport system”). The reactions involved are examples of oxidation-reduction reactions.

 

The very last substance in the chain is oxygen, which accepts the hydrogens and electrons and becomes water (H2O). This is the actual consumption of oxygen that we often measure in exercise physiology (which we will study more in lab sessions).

What is the purpose of this transfer of electrons from NADH2 and FADH2 to oxygen? In this series of oxidation-reduction reactions, chemical energy is made available to power the phosphorylation of ADP. This is usually referred to as “coupling of phosphorylation to oxidation,” or sometimes just “oxidative phosphorylation.”

 

 
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Formation of ATP – Aerobic Metabolism (cont.)

The important points about the ETS may be summarized as follows:

Almost all of the ATP formed in aerobic metabolism is formed by phosphorylation of ADP in the ETS. The energy required to do this comes from coupled oxidation-reduction reactions. The series of oxidation-reduction reactions starts with NADH2 or FADH2 and ends with oxygen being converted to water. 

PAUL can you make these questions in the light blue mouse overs???

Is it possible for ADP phosphorylation to take place without the oxidation-reduction reactions? No, it is not possible. ADP phosphorylation cannot take place without input of energy, and in the ETS this energy has to come from the oxidation-reduction reactions.

Is it possible for the oxidation-reduction reactions of the ETS to take place, with oxygen consumption, without ADP phosphorylation? Yes. This is referred to as uncoupling of oxidation and phosphorylation. When this happens, energy is released from the oxidation-reduction reactions but it is wasted in terms of ATP formation. Some toxic substances kill cells (and sometimes people) by preventing the energy from the oxidation-reduction reactions of the ETS from being used for ADP phosphorylation. Overdoses of aspirin act in this way.

 

 
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Formation of ATP – Aerobic Metabolism (cont.)

You may be asking: Where do the NADH2 and FADH2 (that start the oxidation-reduction reactions of the ETS) come from?

Actually, they come from several places. But most comes from a series of chemical reactions located inside mitochondria close to the ETS and known as the Krebs Cycle (also known as the TCA Cycle and the Citric Acid Cycle).

The Krebs Cycle starts with a reaction that combines the 2-carbon compound acetyl CoA (an extremely important metabolic intermediary compound) with the 4-carbon oxaloacetic acid to make the 6-carbon citric acid. Over a series of nine reactions, the cirtric acid is converted to oxaloacetic acid, partly by “chopping off” two carbons, which are given off as carbon dioxide. (This is where most of the carbon dioxide is formed that we ultimately breathe out via the lungs.) This oxaloacetic acid can then combine with another acetyl CoA to form citric acid to start another cycle of reactions.

In the course of one “turn” of the Krebs Cycle, one ATP is formed (actually it’s a substance known as GTP, but the GTP is converted to ATP). More importantly, in one cycle of the reactions of the Krebs Cycle, one FADH2 and three NADH2 molecules are formed, for use in the ETS. No oxygen is used directly in the Krebs Cycle. But the rate at which the reactions of the Krebs Cycle go is dependent on the rate at which the electrons are transferred from FADH2 and NADH2 to oxygen in the ETS. So, the Krebs Cycle and the ETS work closely together to form ATP as part of aerobic metabolism.

 

 
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Formation of ATP – Aerobic Metabolism (cont.)

A logical next question is:

Where do the 2-carbon acetyl CoA molecules come from to combine with oxaloacetic acid in the first reaction of the Krebs Cycle? Without acetyl CoA, there would be no Krebs Cycle.

In brief, acetyl CoA is formed from the breakdown of the three major foodstuffs: carbohydrates, fats and proteins. Let’s look at these pathways in a little more detail. Then later we will study the relative proportions that these foodstuffs contribute to the energy for ATP formation during exercise.

 

 
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Formation of ATP – Aerobic Metabolism (cont.)

Aerobic catabolism of carbohydrates. Glucose (and other simple sugars) can be broken down to acetyl CoA. In fact, the reactions by which this happens are the same as those of anaerobic glycolysis, except for the final one. In both anaerobic and aerobic glycolysis, one glucose molecule is converted to two pyruvic acid molecules. (Incidentally, biochemists don’t like the term “aerobic glycolysis,” but physiologists often use this term.) In anaerobic glycolysis, each pyruvic acid is converted to a lactic acid molecule in the final reaction. (Remember that this formation of lactic acid is essential for anaerobic glycolysis to continue.) In aerobic catabolism of glucose, each pyruvic acid molecule is instead converted to an acetyl CoA molecule in a single reaction. Besides making acetyl CoA for the Krebs Cycle, this reaction also generates an NADH2 for the ETS. In addition, a carbon dioxide molecule is formed for each 3-carbon pyruvic acid that is converted to a 2-carbon acetyl CoA.

 

There are two other important aspects of aerobic glycolysis: In certain reactions of the pathway, (a) ATPs are formed (a net production of 2-3 per glucose molecule) and (b) an additional two NADH2 molecules (per glucose) are formed, and the electrons from these NADH2 molecules enter the mitochondria to be processed by the ETS.

To summarize, in aerobic glycolysis, glucose from the blood or from stored glycogen is broken down to acetyl CoA (for the Krebs Cycle), and NADH2 (providing electrons for the ETS) and ATP are produced. Carbon dioxide is also produced. No oxygen is used in the reactions of glycolysis. But the reactions that convert glucose to acetyl CoA are dependent on the Krebs Cycle being able to accept the acetyl CoA, and this in turn is dependent on oxygen consumption in the ETS. This makes this pathway of carbohydrate breakdown part of aerobic metabolism.

 

 
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Formation of ATP – Aerobic Metabolism (cont.)

Aerobic catabolism of fats. Fatty acids are the initial substrate for aerobic metabolism of fats. These are the saturated and unsaturated fatty acids that we hear about so frequently related to heart healthy (and unhealthy) nutrition. The basic structural feature of a fatty acid is a chain of carbon atoms bonded together in a row. The most common fatty acids in our diets consist of even numbers of carbon atoms in the chain, usually 16 or 18. Some so-called free fatty acids are carried in the blood attached to plasma proteins. Most fatty acids in the body are part of triglycerides (TGs). A TG molecule has three fatty acids bound to a 3-carbon carbohydrate, glycerol. TGs are stored in adipose (fat) tissue, stored inside muscle fibers, and attached to lipoproteins in the blood plasma. Lipoproteins are large particles consisting of various proteins and fats that serve to transport various fats in the blood. When a muscle fiber needs fatty acid molecules to break down in aerobic catabolism, it can get them from (a) TGs stored in the fiber; (b) free fatty acids in the blood; and (c) TGs attached to lipoproteins in the blood. These fatty acids and TGs in the blood originated either from TGs in adipose tissue or from digested foods.

Breakdown of fatty acids involves a short cycle of four chemical reactions known as beta oxidation. In one cycle of these reactions, a 2-carbon segment of the fatty acid is “broken off” in the form of acetyl CoA. In addition, one NADH2 and one FADH2 are formed. (Actually, there are a couple of exceptions to this, but these are minor for our purposes.) You can see that many acetyl CoA, NADH2 and FADH2 molecules are formed from the breakdown of a single 18-carbon fatty acid.

 

In summary, oxidation of fatty acids provides acetyl CoA for the Krebs Cycle and NADH2 and FADH2 for the ETS. No oxygen is used in the reactions of beta oxidation. But fatty acid oxidation is dependent on the Krebs Cycle being able to use the acetyl CoA, on the ETS being able to use the FADH2 and NADH2, and on oxygen consumption in the ETS. This makes fatty acid catabolism part of aerobic metabolism.

 

 
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Formation of ATP – Aerobic Metabolism (cont.)

Aerobic catabolism of proteins. Proteins are made up of amino acids bonded together. To use protein as a substrate for aerobic metabolism, a protein must first be broken down by enzymes known as proteases, to free up the individual amino acids. Then the nitrogen must be removed from the amino acids. Then, because there are some 20 amino acids, each with its own unique structure, each amino acid must have its own catabolic reaction(s). Ultimately, however, every amino acid can be converted directly or indirectly to acetyl CoA, or to a substance found in the Krebs Cycle. So, after the initial processing of the amino acids, they are broken down to carbon dioxide and water by the same reactions that carbohydrates and fats are. Thus, energy stored in amino acids can ultimately be freed up to form ATP by aerobic metabolism.

NOTE: The purpose of this brief discussion of the aerobic catabolism of proteins is for completeness, to point out that all three of our major dietary foodstuffs can be used as substrate for making ATP by aerobic metabolism. In reality, nearly all of the energy turned over in aerobic metabolism is derived from carbohydrates and fats. We will study the involvement of proteins in energy metabolism in more detail later in this unit.

 

 
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Formation of ATP – Aerobic Metabolism (cont.)

Summary

ATP can be generated by aerobic metabolism using energy ultimately derived from carbohydrates, fats, or proteins. Most of the ATP is formed in the electron transport system (ETS) by the process known as oxidative phosphorylation. Some is also formed in the Krebs Cycle and in glycolysis.

Electrons (attached to hydrogens) are brought to the ETS by NADH2 and FADH2. Then these electrons (+hydrogens) are transferred from one substance to another in a chain of reactions until they are ultimately transferred to oxygen. This converts the oxygen to water. In the process, energy is made available to phosphorylate ADP, forming ATP. The electrons (+hydrogens) brought to the ETS originally come from carbohydrates, fats and proteins. NAD is converted to NADH2 in (a) glycolysis, (b) in the conversion of pyruvic acid to acetyl CoA, (c) in the Krebs Cycle, (d) in beta oxidation of fatty acids, and (e) in the conversion of lactic acid to pyruvic acid. FAD is converted to FADH2 (a) in the Krebs Cycle and (b) in beta oxidation.

The Krebs Cycle requires acetyl CoA as an initial reactant. This acetyl CoA can come from breakdown of fatty acids, sugars, and some amino acids. Products of the Krebs Cycle are ATP (via GTP), NADH2, FADH2, and CO2.

Beta oxidation requires fatty acids as initial substrate. Products of beta oxidation are acetyl CoA, NADH2 and FADH2.

Glycolysis requires sugars, especially glucose, as initial substrate. Products of aerobic glycolysis are ATP, NADH2, and pyruvic acid. The pyruvic acid is then converted to acetyl CoA, with formation of NADH2 and CO2.

After the amino groups have been removed, amino acids from proteins can be substrates for the Krebs Cycle either directly or indirectly.

Endproducts of the aerobic breakdown of all of the initial substrates (carbohydrates, fats, and proteins) are CO2 and H2O. CO2 and H2O have very little energy stored in them. This means that almost every bit of energy is “squeezed out” of the original substrates. Much of this goes to ATP formation. Some is converted to heat.

Of the many chemical reactions that make up aerobic metabolism, oxygen is used in only one – the final reaction of the ETS in which hydrogens are added to oxygen to form water. Without that final reaction, however, all of the reactions of aerobic metabolism would quickly stop. In other words, all of the reactions of beta oxidation, aerobic glycolysis, the Krebs Cycle, and the ETS ultimately depend on oxygen use in the ETS. That is why all of these reactions or pathways are included in “aerobic metabolism.”

 

 
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In the figure below is a summary of all the chemical reactions and pathways involved in ATP formation by aerobic metabolism. Just the major aspects of each pathway are shown, as well as the interrelationships among the pathways.

 
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Formation of ATP – Aerobic Metabolism (cont.)

Advantages and Disadvantages

The big advantage of aerobic metabolism over the other two methods of forming ATP is its huge capacity for ATP formation, that is, total amount of ATP that can be formed.

This is, to a large extent, due to the ability of aerobic metabolism to use carbohydrates, fats and proteins as the initial substrates (whereas the CK reaction is dependent on CP, and anaerobic glycolysis is limited to carbohydrates). Carbohydrates provide the smallest store of energy. In a person of average body size and on a normal mixed diet, a total of about 2,000 kcal of energy is stored in its various forms: glycogen in muscles, glycogen in the liver, and glucose in the blood. In contrast, this same person may have 50,000-100,000 (or more) kcal of energy stored as fat (and a similar amount as protein).

The huge capacity for ATP formation by aerobic metabolism also relates to the nature of the endproducts of these reactions. The endproducts of carbohydrate and fat catabolism are carbon dioxide and water; in addition to these, catabolism of proteins yields nitrogen-containing endproducts, usually urea. The body normally can excrete all of these endproducts easily, so they do not limit aerobic metabolism as lactic acid limits anaerobic glycolysis.

The summary point is that the body has a huge potential for ATP formation by aerobic metabolism, the equivalent of 2,000 kcal or much more. For comparison, recall that the person referred to above has an equivalent of only about 15 kcal of CP in the body, and a maximum of about 50 kcal that can be derived from anaerobic glycolysis.

 

 
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Formation of ATP – Aerobic Metabolism (cont.)

Aerobic metabolism has important limitations, too. Fortunately these are in the areas of the strengths of the other systems.

First, aerobic metabolism absolutely requires oxygen. In reality, oxygen is used directly in only the very last of the long series of reactions. But without oxygen for that last reaction, all of the reactions would quickly stop. This means that formation of ATP by aerobic metabolism is dependent on delivery of oxygen to specific cells (e.g., muscle fibers). If ever the supply of oxygen to a cell is less than what the cell needs, ATP formation by aerobic metabolism will be impaired. (This state of oxygen supply being less than oxygen need or demand is called ischemia.)

The dependence of aerobic metabolism on oxygen delivery to tissues leads to other limitations of this method of ATP formation that are discussed below.

 

 
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Formation of ATP – Aerobic Metabolism (cont.)

The second major limitation of aerobic metabolism is that its maximal power is relatively low, roughly 50% of the maximal power of anaerobic glycolysis and roughly 25% of the maximal power of the CK reaction. This maximal power, sometimes called maximal aerobic power, is closely tied to the whole body’s maximal rate of oxygen consumption (VO2max). As a rule of thumb, 1 liter of oxygen consumed in aerobic metabolism is equivalent to 5 kcal of chemical energy turned over. Therefore, the person with a VO2max of 3.00 L/min can generate ATP in aerobic metabolism at the equivalent rate of up to 15 kcal/min, the person with a VO2max of 4.00 L/min at the rate of up to 20 kcal/min, and so forth. The maximal rate at which aerobic metabolism can make ATP varies a lot among different persons, to a large extent because the capacity for oxygen transport to tissues varies a lot among different individuals and varies with training status.

I need to remind you here that aerobic metabolism can use either carbohydrates or fats as substrate. (Proteins can also be used, but normally carbohydrates and fats make up nearly all of the substrate during exercise. I will address this more later in the course.) Maximal aerobic power is achieved when carbohydrates are the substrate for oxidative metabolism. The highest power with fats as substrate is only about 50% (or less) of the maximal power with carbohydrates as substrate.

As an example, if a person has a VO2max of 3.5 L/min, his/her equivalent maximal aerobic power using carbohydrates as substrate would be (3.5 L O2 / min) x (5 kcal / L O2) = 17.5 kcal/min. In this same person, if only fats were being used as substrate in oxidative metabolism, the maximal rate of energy input would be no more than 8.75 kcal/min. We will study in more detail the involvements of carbohydrates and fats as fuels during exercise later in this unit.

 

 
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Formation of ATP – Aerobic Metabolism (cont.)

A third important limitation of aerobic metabolism in forming ATP during exercise is its slow rate of response. In response to a sudden, big need for ATP formation, such as at the start of a race, the rate at which ATP is formed in oxidative metabolism increases immediately, but the increase is gradual. It takes about 2 minutes for aerobic metabolism to change from its resting rate to its maximal rate of forming ATP. Note the contrast between aerobic metabolism and the other two methods of ATP formation in terms of this characteristic. The CK reaction can instantaneously be at maximal power, and anaerobic glycolysis takes no more than 10-15 seconds to be at maximal power. Even in submaximal exercise that requires oxygen consumption at a rate well below VO2max, the adjustment of aerobic power in the transition from rest to exercise may take 1-2 minutes.

 

 
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Formation of ATP – Summary

The following table presents a summary of the important features of the three methods the body has for forming ATP. The numerical values in the table are typical values for a healthy but not highly trained person of average body size, doing whole-body exercise involving large muscle groups (e.g., running, swimming). Actual values for a given person will depend on body size and composition, type of exercise being done, level and type of training, nutritional status, and other factors.

Mechanisms of ATP Replenishment

CK

Anaerobic Glycolysis

Aerobic
 Metabolism


Oxygen required? No

No 

   Yes 

Toxic endproduct? No lactic acid

carbon dioxide

Substrate(s) CP

glucose

sugars,FFA's,
amino acids


Carbohydrates

Fats

Total capacity (kcal)

15

50

2,000

100,000

Max power (kcal/sec)

1.00

0.50

0.25

0.12

Minimum response time (sec)

0 (Immediate)

15 120

---


 

 
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Review of Lesson

You have come to the end of the online content of Unit 2 - Lesson 1. When you want to review the concepts in this lesson, use the Learning Objectives on Page 1 of this lesson and the Review Questions below. These should be a good study guide. If you can correctly do what the Objectives and Review Questions ask, you will have mastered the most important concepts in this lesson. Please realize, however, that these do not exhaustively cover all the information in the lesson.  

If you are uncertain about any Objective or Review Question, or if you want clarification or expansion of any point in the lesson, I urge you to start a threaded conference discussion on WebBoard. Other students may have the same concerns, will probably benefit from the discussion, and may have the information you seek. And, of course, feel free to contact me (Dr. Eldridge) for assistance.

Be sure to check the Announcements Page to see whether there is a specific WebBoard or other assignment.

Review Questions

1.  Discuss the relationship between catabolism and anabolism.

2.  Discuss how body size and mass of active muscle involved in a bout of exercise affect the ATP-formation methods in terms of maximal power input and capacity for ATP formation.

3.  Draw a single diagram that illustrates the major aspects of aerobic glycolysis, beta oxidation, the Krebs Cycle, and the electron transport system, and how these pathways are related to each other. For each of these, list the substrates (starting chemical substances) and important products related to ATP formation.

4.  Describe the differences between aerobic glycolysis and anaerobic glycolysis.

 
 
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Lesson 2 starts to apply the basics of energy metabolism specifically to exercise. The fundamental question addressed is: How is the energy for the work of exercise specifically provided during exercise of different types (intensities and durations)? 

Learning Objectives

After completion of Lesson 2, the student should be able to:

1. Define the following terms, and be able to use each term appropriately in discussions: respiratory quotient, respiratory exchange ratio, cross-over concept, peptide bond, transamination, transaminase, nitrogen balance equation, nitrogen balance, positive nitrogen balance, negative nitrogen balance, anabolic state, catabolic state, carbohydrate loading.

2. Discuss the relationship between power output and power input during an acute bout of exercise; include one or more absolute principles that are applicable.

3. Discuss the roles of the ATP-formation methods in exercise of different types (intensities and durations). In each case, identify the most likely limitation of each acute bout of exercise if the exercise is limited by metabolism.

4. Compare and contrast carbohydrates and fats as substrates for ATP formation via aerobic metabolism. In doing this, point out the strengths and the weaknesses of these two "aerobic substrates."

5. Describe the effects of exercise intensity and duration on the relative amounts of carbohydrates and fats used as substrates for aerobic metabolism.

6. Discuss the role of proteins as substrate for ATP formation via aerobic metabolism in (a) a person with normal nutritional status and (b) a starving person.

7. Discuss some of the dietary regimens that can affect energy metabolism during acute exercise.  

Outline of Content  

III.  Formation of ATP during exercise

   A.  Principles

   B.  Application of principles – Analysis of specific activities

      1.  Running a marathon in 3 hours

      2.  Running 100 meters in 12.00 seconds

   C.  Summary – Potential metabolic limitations of exercise

IV.  Carbohydrates, fats and proteins as substrates
         for aerobic metabolism

   A.  Carbohydrates and fats – Contrasts; advantages
         and limitations

   B.  Effect of exercise intensity on proportions
         of carbohydrates and fats used

   C.  Effect of exercise duration on proportions of
         carbohydrates and fats used

   D.  Protein use

   E.  Effect of diet 

 

 

 

 
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Formation of ATP During Exercise

In the last section of the previous lesson, I dealt with basic characteristics of the three methods for replenishing ATP as it is used. In this section I want to address the application to acute bouts of exercise. To maximize performance by an athlete, it is critical to analyze the metabolic requirements of the specific activity the athlete does in competition and to determine potential metabolic limitations of performance. Then this must be applied to performance itself and to training.

There are two essential considerations:

(a) Where does the energy come from to form the required ATP over the course of the entire performance?

(b) Where does the energy come from to form the required ATP during transitions from low intensity to high intensity exercise? The most obvious examples of these transitions are the starts of running races, in which athletes change very quickly from essentially resting at the start to high or even maximal power. Other transitions occur during the races, but they involve smaller changes in power.

 

 
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Formation of ATP During Exercise (cont.)

There are several absolute principles that apply:

(a) The major determinant of the rate of energy input needed at a given instant during a given activity is the power output (i.e., the intensity of the exercise). If the power output changes, so does the power input.

(b) The power input required for a given activity has to be matched by the actual power input at every instant of the activity; it’s a pay-as-you-go system. The instant actual power input fails to meet what is needed, the person must decrease the intensity of the exercise.

Example: Assume that for a given athlete to run at 15.0 mph (i.e., a 4-minute-per-mile pace), energy is required at the rate of 0.5 kcal/sec (30.0 kcal/min), to replenish the ATP so that the active muscle fibers do not run out. If this runner is running at 15 mph, it is absolutely certain that his/her metabolic energy input is 0.5 kcal/sec. If that power input would fall to 0.4 (or even 0.49) kcal/sec, it is just as certain that this runner is NOT running at 15.0 mph.

 

 
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Formation of ATP During Exercise (cont.)  

Absolute Principles (cont.)

 (c) At any instant in time, the total rate at which energy is turned over (i.e., total power input) is the sum of the individual rates of the three systems:

Total Rate = Rate of CK + Rate of glycolysis + Rate of oxidative metabolism.

EXAMPLE: Using the example of running at a 4-minute-per-mile pace with energy being required at the rate of 0.5 kcal/sec, the following table lists four (of an infinite number of) possible combinations of contributions of the three methods of ATP replenishment.

Power Input (kcal/sec)

CK Reaction Anaerobic
Glycolysis
Aerobic
Metabolism
Total

 

0.45 0.04 0.01 0.50
0.25 0.20 0.05 0.50
0.10 0.30 0.10 0.50
0.00 0.10 0.40 0.50

Each of these is a realistic possibility for specific portions of the mile race. For the given point of time in the race, it doesn’t matter how the total power input is divided up among the methods; what matters is the total. (How the total is divided up may matter a great deal, however, in terms of the entire exercise period, if the result is depletion of CP or accumulation of too much lactic acid.)

 

 
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Formation of ATP During Exercise (cont.)

Absolute Principles (cont.)

(d) In general, especially over the long term, the body prefers aerobic metabolism as the method for replenishing ATP. This is because the body has such a large supply of energy that can be transferred this way and without producing endproducts that create problems. But the relatively slow rate of response and relatively slow maximal rate of ATP formation by aerobic metabolism necessitate involvement of other systems (i) during transitions from lower to higher exercise intensities and (ii) during exercise of high intensity.

(e) Because of its relatively low energy capacity, the body tries to spare the CK reaction, using it only when the other two methods can’t meet the requirement.

(f) During transitions from lower to higher exercise intensities (and therefore from lower to higher power inputs), all three methods contribute to the total energy input (i.e., to formation of ATP), although not in equal amounts.

NOTE: All three methods are “switched on” in response to the increased demand. It is NOT a matter of one method being turned on to provide the energy, working alone for awhile, and then switching off as another switches on.

(g) In every bout of acute exercise, all three methods contribute to ATP formation during the activity, but the relative contribution of each method varies with the intensity and duration of the exercise.

 

 
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Formation of ATP During Exercise (cont.)

Before we apply these principles to specific exercise examples, I need to emphasize a couple of points about very-high-power activities that last less than about 3 seconds. Examples of these activities include a maximal vertical jump, putting the shot, and swinging a baseball bat with maximal force. These activities require the highest (or nearly highest) rates of power output and input the body or individual muscle groups can have. But these activities are so brief they can be done using only the ATP in the muscles at the start of the activity. Replenishment of the ATP during the activity is not a factor in performance. Replenishment becomes a factor if such activities have to be repeated in rapid succession, such as repeated jumps for rebounds in basketball or repeated swings of a bat during an at bat in baseball or softball. But during a single performance there is no need for replenishing ATP. In the discussion that follows, I will not include these very short activities. I will focus only on activities for which the muscle does not have enough stored ATP at the start, and therefore activities that must have replenishment of ATP during the exercise. Such activities can be limited by the rate at which ATP is formed.

 

 
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Formation of ATP During Exercise (cont.)

Now let’s apply the principles listed on previous pages to specific exercise examples. Running races of different distances provide good examples. Let’s analyze the same runner in different races. For simplicity, let’s assume this runner has the following metabolic characteristics:


CK Reaction Anaerobic Glycolysis Aerobic Metabolism of Carbohydrates

Maximal Power

(kcal/sec)

1.00 0.67 0.33

(kcal/min)

60 40 20

Capacity
  (total kcal for
   ATP formation)

15 60 2,500

Note that these values are not identical to the summary “textbook values” given previously. Remember that those values were given as typical guidelines, and actual values vary from one person to another. The runner we are dealing with here may represent a larger person and/or a more highly trained person, though not elite or even highly competitive.

 

 
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Formation of ATP During Exercise (cont.)

Let’s start with our runner running a marathon in exactly 3 hours. (This is far from the world’s best, but if you haven’t tried it, don’t knock it!) This is an average pace of about 8.7 mph (a little less than 7 minutes per mile; 233 m/min; 3.89 m/sec). For simplicity, let’s assume that this runner maintains this pace exactly over the entire 26 miles 385 yards (42.2 km). This pace requires a total power input of 0.25 kcal/sec (15.0 kcal/min) and therefore a total of 2,700 kcal over the entire race. Let be remind for emphasis that this runner absolutely must turn over energy at the rate of 0.25 kcal/sec every second that he runs at this speed.

The required power input can be provided by aerobic metabolism, since the runner’s maximal aerobic power = 0.33 kcal/sec (20 kcal/min). In fact, this pace requires 75% of the runner’s maximal aerobic power. In the first 2 minutes of the race, however, aerobic metabolism cannot meet the demand, because it adjusts slowly to demand. Aerobic metabolism would start forming ATP at a faster rate the instant the race starts, but it would take a couple of minutes for it to adjust to the 15.0 kcal/min required.

For example, the energy input from aerobic metabolism might be 0.033 kcal/sec (2 kcal/min) during the first 15 seconds, 0.09 kcal/sec (5.4 kcal/min) from 0:15 to 0:30, 0.14 kcal/sec (8.4 kcal/min) from 0:30 to 0:45 and so on until leveling off at 0.25 kcal/sec (15 kcal/min) by about 2:00. During this time, the total power input of 0.25 kcal/sec (15 kcal/min) still has to be provided for this runner to run at 8.7 mph. And it is provided by adding contributions from the CK reaction and anaerobic glycolysis.

In the first few seconds of the race, while aerobic metabolism and glycolysis are adjusting, almost all of the ATP is replenished by the CK reaction, because it adjusts instantaneously. By about 15 seconds, glycolysis has adjusted, so this system can provide what is needed beyond what aerobic metabolism can provide. At this point, the CK reaction can stop making ATP and thus spare the CP in case it is needed later. So, if aerobic metabolism is forming ATP at the equivalent rates given above, the input from glycolysis from 0:15 to 0:30 will be 0.16 kcal/sec (9.6 kcal/min), and from 0:30 to 0:45 will be 0.11 kcal/sec (6.6 kcal/min), providing for the 0.25 kcal/sec (15 kcal/min) required. The input from glycolysis will gradually decrease as the input from oxidative metabolism increases. At 2:00, when the total demand is being met by oxidative metabolism, glycolysis can stop making ATP.

The graph depicts the contributions of the three methods of ATP replenishment during the first 3 minutes of the runner’s marathon, divided into 15-second segments.

 

 
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Formation of ATP During Exercise (cont.)

Note that in this analysis of this runner’s energy metabolism during the marathon, I am oversimplifying to emphasize the concepts regarding the involvement of the three ATP replenishment systems during exercise. In actuality, there would still be some anaerobic glycolysis occurring in this runner throughout the race, but the net amount of ATP formed this way is very small. I will address this topic more later. For now, I hope it is obvious that a runner simply cannot have much lactic acid accumulation if he/she is going to run for 3 hours. Remember that the total capacity of anaerobic glycolysis is only 60 kcal in our runner, and a total of 2,700 kcal is needed over the entire race.

Considering the entire 3-hour marathon, a few kilocalories of energy are turned over in the CK reaction and by glycolysis at the very start to supplement aerobic metabolism. But over the entire race, almost all of the 2,700 kcal would be turned over in aerobic metabolism. Over 99% of the energy input for this marathon race is provided by aerobic metabolism and less than 1% from anaerobic metabolism (CK + glycolysis). Note, however, that it is not 100% from aerobic metabolism. Anaerobic mechanisms played an absolutely essential role at the start of the race. Also, if this runner had made any sudden increases in pace at other times during the race, small inputs from the anaerobic mechanisms would have been needed until oxidative metabolism adjusted.

 
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Formation of ATP During Exercise (cont.)

Let’s consider possible metabolic limitations confronting this runner during the 3-hour marathon. Depletion of CP is not a factor since the CK reaction contributes only a small amount to power input, at the start of the race (and a little at other times if the runner had accelerated during the race). Similarly, lactic acidosis is not a factor since anaerobic glycolysis contributes only a small amount to power input. The major concern is depletion of glycogen stored in the fibers of the muscles of the legs involved in running. This glycogen is the major substrate for aerobic metabolism in this 3-hour race, although some fat would also be used. If the glycogen would be totally depleted at some point before finishing the marathon, the runner would be dependent on fat as the substrate for aerobic metabolism from that point on. As a consequence, he would have to slow his running speed greatly, because the potential power input from fat is no more than 50% of the maximal power from carbohydrates. The fact that our runner maintained his power input at 75% of maximum throughout the 3-hour race verifies that he did not run out of muscle glycogen.

 

 
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Formation of ATP During Exercise (cont.)

Now let’s analyze the energy turnover of the same runner during a sprint of 100 meters in 12 seconds. (No world record here either, but our runner is doing the best he/she can!) This is an average speed of 8.33 m/sec (18.6 mph). As with our analysis of the marathon run, for simplicity, let’s assume that this runner is able to maintain this constant speed throughout the race (although we know this is impossible, because of the acceleration required from a “standing” start. In reality this runner would be running slower than the average speed early in the race and faster than the average speed at the end). This running speed is more than twice the speed of running a marathon in 3 hours, and the required power input is more than twice as much also. Let’s assume this 100-meter pace requires 0.6 kcal/sec (36 kcal/min; 7.2 kcal total over the 12 seconds). In other words, if ever the runner’s power input falls below 0.6 kcal/sec, he will no longer be running at 8.33 m/sec.

 

 
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Formation of ATP During Exercise (cont.)

First, let’s ask whether aerobic metabolism can meet this demand. The answer is “no” for two reasons:

(a) This runner’s maximal aerobic power is 0.33 kcal/sec, so even if it were at maximum it could not meet the demand.

(b) The rate of energy turnover from aerobic metabolism increases slowly at the start of exercise, and it may take 2 minutes for aerobic power input to adjust completely. The 12 seconds of this race is not nearly enough time for complete adjustment.

Does this mean that aerobic metabolism does not contribute at all to this bout of exercise? No, aerobic metabolism does contribute. Let’s assume that aerobic power input has increased to 33% of its maximal value during the 12th second, that is, 0.11 kcal/sec. This would be only one-sixth of the total requirement during the 12th second, and of course the contribution from aerobic metabolism would be less than that in the previous 11 seconds. So, the contribution of aerobic metabolism to the total required over the 12 seconds is small, but it is not zero.

 

 
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Formation of ATP During Exercise (cont.)

What about the contribution of anaerobic glycolysis? The runner’s maximal glycolytic power is 0.67 kcal/sec, so glycolysis is capable of meeting the total power input required. But, anaerobic glycolysis may take 10-15 seconds after the start of exercise to adjust. So, it is possible that in the last couple of seconds of the 100-m race, glycolysis is providing most of the energy for ATP replenishment (remember that aerobic metabolism is providing a little). But while the rate of glycolysis is increasing during the first 10 seconds or so, the power input from glycolysis and aerobic metabolism combined is less than the required 0.6 kcal/sec. The additional power needed must come from the CK reaction.

What is the contribution of the CK reaction? Immediately after the runner starts, nearly all of the required 0.6 kcal/sec must be provided by the CK reaction while aerobic metabolism and especially anaerobic glycolysis are adjusting. Remember that the CK reaction can adjust instantaneously to its maximal power, if needed. And in this case, the required power is well below the maximal power of the CK reaction (i.e., 1.0 kcal/sec). So the CK reaction can easily meet the required power at the start. In fact, it could meet the entire power input over the entire 12-second period. It doesn’t need to, however, since the combined contribution of aerobic metabolism and anaerobic glycolysis increases with each second of the race. Therefore, the energy turnover in the CK reaction is highest immediately after the start of the race and then gradually decreases the rest of the time. In the last couple of seconds, if glycolysis and aerobic metabolism are meeting the entire demand, the contribution from the CK reaction would be zero.

The figure presents a second-by-second analysis of the runner’s power input during the 12-second 100-meter sprint.

 

 
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Formation of ATP During Exercise (cont.)

Was there a metabolic limitation for this runner in this 100-meter race? Based on our simplified analysis, probably not. Certainly 12 seconds is not nearly long enough for muscle glycogen to be depleted via glycolysis (anaerobic and aerobic). What about lactic acidosis? There would certainly be some acidosis because of the high rate of glycolysis, especially near the end of the run. But more than 12 seconds of high glycolytic activity is needed to have maximal or near-maximal levels of lactic acid accumulation. That leaves the possibility of a limitation related to the CK reaction. Was muscle CP depleted? No. Even if the CK reaction had provided all of the energy for the entire run (i.e., 7.2 kcal), this would not have depleted the CP. This runner had the equivalent of 15 kcal of CP stored in his muscles at the start of the race, available for transfer of energy to ADP via the CK reaction. So, at the end of this race, the runner’s muscle CP concentration was reduced, but it was not totally depleted.

REMEMBER: The very fact that this runner did this exercise (i.e., ran at 8.33 m/sec for 12 seconds verifies that there was no metabolic limitation. He absolutely had to be providing the required energy via metabolism.

Is it possible that this runner could have a metabolic limitation to running 100 meters in 10 seconds? Absolutely.

 

 
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Formation of ATP During Exercise (cont.)

Let me highlight key concepts we have been dealing with in this section.

During every bout of acute exercise, some of the energy input for making ATP comes from each of the three methods. But the contribution of each method varies from a fraction of a percent to a very high percentage, depending especially on the intensity of the exercise. The following table presents examples of the contributions of the ATP replenishment methods to maximal-effort exercise of various durations. Obviously, a person can exercise at very high intensities for very brief periods, and the intensity must be decreased if exercise is to be prolonged. Therefore, in the table, the absolute intensity of the exercise goes down as the duration increases.

                      Contribution to Total Power Input


Exercise Duration CK Reaction Anaerobic Glycolysis Aerobic Metabolism

5 seconds 95% 4% 1%
10 seconds 65% 25% 10%
1 minute 20% 50% 30%
2 minutes 10% 40% 50%
4 minutes 5% 25% 70%
10 minutes 2% 8% 90%
30 minutes 1% 4% 95%
60 minutes <1% <2% 98%

 
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Formation of ATP During Exercise (cont.)

A coach and athlete should use this table and the concepts it summarizes to analyze specific activities, in order to estimate the contributions of the different metabolic methods of ATP replenishment. This does two things.

First, it tells what is most likely to be limiting, from the point of view of muscular ability to replenish ATP.

(NOTE: I am not saying here that it is always a limitation of metabolism in active muscles that limits performance. Such metabolic factors are only one category of factors that can limit performance. Many other things can limit performance too.)

In general:

  • Very high power activities of about 15-30 seconds in duration are most likely to be limited by depletion of CP in muscles.  

  • High power activities of about 1-10 minutes are most susceptible to limitation by lactic acid build-up in active muscles (activities of longer duration can be too, but the longer the duration the less likely it is for acidosis per se to be limiting).  

  • Activities of 1-3 hours are often limited by availability of glycogen in active muscles. Long-duration activities may also be limited by availability of glycogen in the liver. Liver glycogen supplies glucose to the blood. When liver glycogen gets too low, blood glucose concentration falls (hypoglycemia), and central nervous system symptoms such as dizziness, light-headedness, disorientation and even fainting may occur. (More about this later.)

A second use of analyzing activities in terms of contributions of the methods of ATP replenishment: As the basis for making decisions about proportion of training time to spend on different types of training. For example, if an athlete competes in an activity in which 10% of the energy is provided by the CP method, 40% by glycolysis, and 50% by aerobic metabolism, most training should be spent with exercise that stress glycolysis and aerobic metabolism. HOWEVER, exercise that stresses the CP method cannot be totally ignored. Furthermore, if the athlete is already “strong” in terms of aerobic metabolism and relatively weak in terms of glycolysis, the training may be adjusted to improve the weaker area (but obviously without weakening the strong area).

 

 
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Formation of ATP During Exercise (cont.)

The graph below shows the analysis of maximal-effort activities of different durations based on contributions of aerobic metabolism and anaerobic metabolism to ATP formation during the exercise. Note that the CK reaction and glycolysis are combined into a single anaerobic metabolism category.

You can see from this that, as a general guideline, maximal-effort exercise that is about 2 minutes in duration is about 50:50; that is, about 50% of the ATP is provided by aerobic metabolism and about 50% by anaerobic metabolism. Almost 100% of ATP replenishment during maximal-effort exercise of 10 seconds or so comes from anaerobic methods, and almost 100% of ATP replenishment during maximal-effort exercise of 60 minutes and longer comes from aerobic metabolism.

 

 
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Formation of ATP During Exercise (cont.)

I want to emphasize several points about the graph on the previous page and about the breakdown of activities based on the source of ATP replenishment.

  • The percentages presented are general guidelines; they are not absolute in all cases. For example, it is very useful to remember that with maximal-effort exercise, about half of the energy for ATP replenishment during the exercise comes from aerobic metabolism and about half from anaerobic metabolism when the exercise is about 2 minutes in duration. But this could occur with exercise that is less than 2:00 in some individuals and more than 2:00 in others. This is an approximation.  

  • These breakdowns are dealing with energy that is provided during the exercise, and they do not include the recovery period. We will deal with metabolism in recovery in more detail later. For now you should realize that energy during recovery is essentially completely provided by aerobic metabolism. It is the contributions of the three ATP replenishment methods during exercise that determines whether they limit performance. Recovery cannot limit prior performance (though it may be a factor in subsequent performance)!  

  • These breakdowns have referred to maximal-effort exercise. If the same exercise is done submaximally, the percent contributions of the ATP replenishment methods will be shifted towards a relatively higher value for aerobic metabolism and proportionately lower values for the anaerobic mechanisms. For example, let’s assume that a given person’s PR (personal record) for running 800 m is 2:00. When this runner runs 800 m in 2:00, it is maximal effort, and about 50% of the energy for ATP formation during the exercise comes from aerobic metabolism and about 50% from anaerobic metabolism. When this same runner jogs 800 m in 3:30, this is far below a maximal effort, and much more than 50% of the energy for ATP formation during this 800-m jog comes from aerobic metabolism and much less than 50% from anaerobic metabolism.

 

 
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Carbohydrates, Fats and Proteins as Substrates for Aerobic Metabolism

In this section we will study the contributions of the various foodstuffs as substrates or starting fuels for aerobic metabolism. With the anaerobic methods there are no options for substrates for ATP replenishment; the CK reaction must use CP, and glycolysis must use carbohydrates. But aerobic metabolism can use carbohydrates, fats, or proteins. In normal persons in normal nutritional states, proteins provide less than 10% of the energy for aerobic ATP replenishment during exercise. In other words, carbohydrates and fats account for over 90% of aerobic ATP replenishment. Let’s study the contributions of these two predominant substrates first. Please remember that we are dealing only with aerobic metabolism in this section.

 

 
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Carbohydrates, Fats and Proteins as Substrates for Aerobic Metabolism (cont.)

Let’s contrast carbohydrates and fats as substrates for aerobic metabolism, to see the advantages and disadvantages of each:

1) Maximal rates of aerobic ATP synthesis – ATP can be formed at least twice as fast with carbohydrates as the substrate than with fats as substrate. This has implications for the relative use of carbohydrates and fats depending on exercise intensity (explained more below).

2) Energy densities – Nine kilocalories of energy is stored in 1 gram of fat, and 4 kcal in 1 gram of carbohydrate. Thus, fats are far superior to carbohydrates as a compact storage form of energy. Each of us would have to weigh a lot more if we had no storage fat and had the same amount of energy stored as glycogen.

3) Total body stores (i.e., total energy potentially available) – Adults typically have about 1,000-3,000 kcal of energy stored as carbohydrates, mostly as glycogen in skeletal muscles. (This is not including periods of glycogen depletion after prolonged exercise.) The exact amount depends on body size and amount of muscle mass, diet, and training program. In contrast, adults will have tens of thousands (some even more than 100,000) of kilocalories of energy stored as fat, primarily in adipose tissue under the skin and around internal organs. Even a lean athlete will have much more energy stored as fat than as carbohydrate. For example, a 100-pound (45.4 kg) gymnast who is 6% fat has 2.72 kg (2,720 grams) of fat. This is equivalent to 24,480 kcal of energy (2,720 g x 9 kcal/g).

 

 
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Inline Problem....A football Lineman who weighs 344 lb.and is 28% fat. How much energy does he have stored as fat? Answer: 39,404 kcal
 
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Carbohydrates, Fats and Proteins as Substrates for Aerobic Metabolism (cont.)

Contrast between carbohydrates and fats (cont.):

4) Amount of ATP formed per amount of oxygen consumed – When carbohydrates are completely broken down (oxidized), 5.05 kcal of energy are made available for every liter of oxygen consumed. In contrast, fat yields 4.69 kcal/L oxygen. Thus, carbohydrates make more effective use of oxygen consumption in transferring energy to ATP. This also has implications regarding use of these substrates at different exercise intensities (see below). When we are nearing the limits of our capacity for transport and use of oxygen (i.e., VO2max), it is metabolically advantageous to use carbohydrates as substrate to get the most energy per unit of oxygen consumed.

 

 
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U2L2P23 - Inline quiz about amount of energy for a given VO2 if 100% CHO vs. 100% Fat as fuel.  Assume that a person is consuming 3.00 L of oxygen per minute. What would this person’s aerobic power input be if (a) using 100% fat as substrate and (b) if using 100% carbohydrate as substrate?ANSWER: 14.1 kcal/min if 100% fat; 15.2 kcal/min if 100% carbohydrate. One implication of this is that at the same VO2, this person could exercise at a power that is 8% higher if 100% carbohydrate was the substrate compared with 100% fat.
 
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Carbohydrates, Fats and Proteins as Substrates for Aerobic Metabolism (cont.)

Contrast between carbohydrates and fats (cont.):

5) Amount of carbon dioxide formed per amount of oxygen consumed – When carbohydrates are completely oxidized, exactly the same volume of carbon dioxide is produced as the volume of oxygen consumed. When fats are completely oxidized, the volume of carbon dioxide produced is only 70% of the volume of oxygen consumed. This ratio of VCO2 to VO2 is referred to as the respiratory quotient (RQ) when analyzing cellular metabolism. In other words, the RQ of carbohydrates is 1.00 and the RQ of fats is 0.70. (Actually, the value for fats varies from 0.68 to 0.71, depending on the exact form of fat, but on average it is 0.70). This information can be used in the laboratory to determine the percentages of carbohydrates and fats used as fuel by the whole body during certain resting and exercise conditions. When we calculate the VCO2/VO2 ratio of the whole body, we use the term respiratory exchange ratio (abbreviated RER or R). Briefly, when steady-state conditions exist, an RER value of 0.85 indicates that carbohydrates and fats are contributing equally as substrates for aerobic metabolism. As the RER gets closer to 1.00, the percent contribution of carbohydrates increases and percent contribution of fats decreases; as the RER gets closer to 0.70, the percent contribution of fats increases and percent contribution of carbohydrates decreases. This is a powerful tool in the laboratory for assessing carbohydrate and fat metabolism.

One might question whether the extra carbon dioxide produced (per volume of oxygen consumed) with carbohydrate metabolism compared with fat metabolism presents a problem. It doesn’t for people with normal lung function; this “extra” carbon dioxide is easily excreted via the lungs. Individuals with certain lung diseases, however, have difficulty excreting carbon dioxide. In extreme cases, high fat diets would actually benefit such persons by reducing the amount of carbon dioxide produced in aerobic metabolism.

 

 
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Carbohydrates, Fats and Proteins as Substrates for Aerobic Metabolism (cont.)

Effect of Exercise Intensity on Relative Proportions of Carbohydrates and Fats Used as Substrate for Aerobic Metabolism

In principle, the ratio of carbohydrate utilization to fat utilization is directly related to the intensity of exercise. There is a “50-50-50 rule of thumb”: When exercise intensity is 50% of VO2max, 50% of the substrate for aerobic metabolism is carbohydrate and 50% is fat. (NOTE: As with all “rules of thumb,” these numbers are not absolutes; they are typical values. Actual values vary from person to person and in different situations, depending on a number of factors.) This relationship is depicted in the graph.

The term cross-over concept has been applied to this relationship. At low exercise intensities (less than 50% of VO2max), more fat is used in aerobic metabolism than carbohydrate. That is, the ratio of carbohydrate to fat is less than 1.0. As exercise intensity is increased, this ratio increases. At about 50% of VO2max there is a “cross-over.” The proportion changes from more fat than carbohydrate to more carbohydrate than fat; the ratio of carbohydrate to fat utilized becomes greater than 1.0.

 
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Carbohydrates, Fats and Proteins as Substrates for Aerobic Metabolism

Effect of Exercise Intensity on Relative Proportions of Carbohydrates and Fats Used as Substrate for Aerobic Metabolism (cont.)

There is probably no situation in which either fat or carbohydrate makes up 100% of the substrate. In principle, however, at rest and during low-intensity exercise, much more fat is used than carbohydrate; and at very high exercise intensities, much more carbohydrate is used than fat. As with everything in physiology (even if we don’t yet recognize it), there is logic to this. When power input needs to be high, carbohydrates are preferred because the maximal rate of ATP formation is much higher with carbohydrate as substrate than with fat as substrate. And more energy is turned over per volume of oxygen consumed with carbohydrate as substrate (oxygen transport has a limit that is stressed during high intensity exercise). When the demand for power input is low, fat metabolism can meet the demand, even with its slower rate of ATP formation, and the concern about effective use of the oxygen consumed is less because the overall rate of oxygen consumption is well below the limits of the oxygen transport system. The big advantage of using fats rather than carbohydrates whenever possible is that there is, for all practical purposes, an unlimited supply of energy from fats. This is not true for carbohydrates. This use of fats at lower exercise intensities is one example of what is often referred to as glycogen sparing. The body does many things to try to spare glycogen, because it is in rather low supply and because its use is critical in higher intensity exercise.

 

 
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Carbohydrates, Fats and Proteins as Substrates for Aerobic Metabolism (cont.)

As we have discussed, the relative proportion of fats used as substrate for aerobic metabolism is inversely related to exercise intensity (i.e., higher percentage of fats used at lower intensities and lower percentage of fats used at higher intensities). Because of this, it is common to hear fitness and weight-management “experts” advise that the best exercise for burning fat is very low intensity exercise. This is an oversimplification, and in many cases it is not true.

Two factors determine the number of calories derived from fats during exercise: (a) The percentage of the total power input derived from fats and (b) the total power input. So, as the exercise intensity increases, it is true that the percentage of energy derived from fat decreases, but the total energy input per minute increases. Therefore, energy from fat is a smaller percentage of a larger value. So, often the rate at which energy is derived from fat is about the same or may even be greater at higher exercise intensities.

What’s the best advice? IF a person is going to exercise for a given distance (e.g., walk or run 1 mile) or total caloric expenditure (e.g., 200 or 300 kcal), then more total energy is derived from fats at lower intensities than at higher intensities. But IF a person is going to exercise for a given period of time (e.g., 30 minutes), more total energy is derived from fats at higher intensities than at lower intensities. Most people in fitness and weight-loss programs have a given period of time for exercise. In such cases, a person “burns” more total fat exercising at the highest intensity he/she can tolerate for the given time period. Please note that this is only considering the calories derived from fat. Other factors must be considered when prescribing exercise intensity (e.g., cardiovascular limitations, risk of injury, motivation of the exerciser).

 

 
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Carbohydrates, Fats and Proteins as Substrates for Aerobic Metabolism (cont.)

Effect of Exercise Duration on Relative Proportions of Carbohydrates and Fats Used as Substrate for Aerobic Metabolism

The intensity of exercise (power output) is the primary determinant of the relative contributions of fats and carbohydrates as substrates for aerobic power input. But the duration of exercise affects this too. For one thing, no matter what the intensity of exercise, there is typically a relatively high use of carbohydrates during the first few minutes of exercise, during the period of transition from low energy demand at rest to the higher energy demand of the exercise. Of greater significance, during prolonged exercise, after at least 30 minutes, the ratio of carbohydrate use to fat use gradually decreases as exercise continues. For example, if 60% of the energy from aerobic metabolism was derived from carbohydrates and 40% from fats during the first 20-30 minutes of exercise (a carbohydrate-to-fat ratio set by the exercise intensity), these values may be 55% carbohydrate and 45% fat after 1 hour, and 50% carbohydrate and 50% fat after 2 hours. You can see that this is another example of glycogen sparing. As exercise goes on for a long period of time, there is more and more risk of depleting glycogen stores. To decrease this risk, the body shifts to use of relatively more fat and relatively less carbohydrate, compared to the earlier values (not necessarily more fat than carbohydrate).

The effect of exercise duration on the relative use of carbohydrates and fats may be thought of as being superimposed on the major determinant of substrate use, the intensity of the exercise.

 

 
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Carbohydrates, Fats and Proteins as Substrates for Aerobic Metabolism (cont.)

Protein Use

Proteins are in general very large molecules, made up of many amino acids bonded together by peptide bonds. There are approximately 20 amino acids in the body, and each has a unique chemical structure. But there is one characteristic feature of all amino acids: one carbon atom has both an amino group (-NH2) and an organic acid group (-COOH) attached to it. A peptide bond is a specific type of chemical bond connecting the carbon of the acid group of one amino acid to the nitrogen of the amino group of another amino acid.

There are very many proteins in the body, and they fall into various functional categories: enzymes (e.g., CK, ATPase), hormones (e.g., insulin), structural material (e.g., collagen of connective tissue), mechanics (e.g., the muscle proteins, actin and myosin), transport (e.g., hemoglobin and albumin in the blood), defense (e.g., antibodies, blood coagulation factors), and substrate for energy metabolism. The focus of this brief section is on the use of proteins as substrate for energy metabolism.

 

 
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Carbohydrates, Fats and Proteins as Substrates for Aerobic Metabolism

Protein Use (cont.)

The many carbon-carbon bonds that exist in amino acids have energy similar to the carbon-carbon bonds that are in fatty acids and sugars. Therefore, there is potentially a huge supply of energy available in the form of proteins in the body, as much as or more than the energy stored in fat, depending on a person’s nutritional state and body composition. Because most proteins serve important functions in the body, use of proteins as substrate for energy metabolism could compromise critical functions. In spite of this, and even though the body normally has a huge supply of energy stored as fat, some proteins (amino acids) are catabolized in exercise.

Amino acids can be substrates for aerobic metabolism, but not anaerobic metabolism. During low-intensity exercise, perhaps 2-3% of the ATP formed in aerobic metabolism is derived from amino acid breakdown. During high-intensity exercise, or during the later stages of prolonged exercise, this percentage may be 5-10%. So the relative contribution of amino acids to aerobic energy metabolism is small. But remember that a given power input is required for every exercise intensity, and every contribution to the total is essential.

 

 
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Carbohydrates, Fats and Proteins as Substrates for Aerobic Metabolism

Protein Use (cont.)

How are amino acids used for ATP formation? Amino acids that are parts of proteins must first be freed. This is accomplished by enzymes called proteases, which break the peptide bonds. Then the nitrogen-containing amino groups must be removed. In skeletal muscle, this is done by the process called transamination, catalyzed by enzymes known as transaminases. In transaminase reactions, the amino group is transferred to another molecule and replaced with a keto group (C=O). In the most common transaminase reaction, an amino acid reacts with pyruvic acid. The keto group from the pyruvic acid is transferred to the amino acid, and the amino group from the amino acid is transferred to pyruvic acid in exchange. In the process, pyruvic acid becomes the amino acid alanine. This may appear to accomplish nothing, since we have simply exchanged one amino acid for another. But this reaction collects amino groups from many different amino acids into a single form, alanine, and this alanine can be processed further. For example, alanine can be put into the blood and carried to the liver, which can use it to make glucose (which is discussed further later in this unit). After the amino acids are freed of their amino groups (and become keto acids), they are converted to various substances that are in the normal pathways of aerobic metabolism. These include pyruvic acid, acetyl CoA, and various substances in the Krebs Cycle, depending on the specific amino acids.

Skeletal muscles have fairly high levels of transaminase activity. They seem to prefer using branched-chain amino acids as substrate for aerobic metabolism, but they can use any amino acid as substrate.

 

 
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Carbohydrates, Fats and Proteins as Substrates for Aerobic Metabolism

Protein Use (cont.)

Proteins in the body are constantly turning over. That is, "old" ones are broken down and replaced by "new" proteins. Various proteins differ in rates of turnover, and many turn over very slowly. Nevertheless, there is constant breaking down and building up of proteins in the body.

Nutritional status with reference to protein intake and breakdown is described by the nitrogen balance equation. Nearly all of the nitrogen ingested in the diet, "stored" in the body, and excreted by the body is or was part of amino acids attached to proteins. Therefore, protein nutritional status can be described by the relationship between nitrogen taken in (NIN) and nitrogen put out (NOUT).

When NIN = NOUT, exactly the same amount of nitrogen is being excreted as the amount of nitrogen ingested. In this state the person is in nitrogen balance. On the whole, this indicates that there is no net build-up of tissue protein nor net breakdown of proteins.

When NIN > NOUT, more nitrogen is being taken in than is being excreted. This is referred to as positive nitrogen balance. This is evidence of an anabolic state with more tissue protein being formed than is being broken down. This is the normal state during developmental growth spurts. It is also the desired state of athletes who are trying to build muscle mass.

When NIN < NOUT, more nitrogen is being excreted than is being taken in the diet. This is referred to as negative nitrogen balance. This is evidence of a catabolic state with more tissue protein being broken down than is being formed. This state is not normally desirable, especially in athletes. A general catabolic state occurs with muscle wasting diseases, such as muscular dystrophy, and with aging after a certain age (especially in sedentary people).

 

 
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Carbohydrates, Fats and Proteins as Substrates for Aerobic Metabolism
Protein Use (cont.)

What are guidelines related to dietary protein requirements?

Several decades ago, the general rule in terms of dietary intake was: 1 gram of protein per kilogram of body weight per day. Based on that guideline, a 60-kg person should take in 60 g of protein a day, a 70-kg person should take in 70 g per day, etc. Most nutritionists agreed that this was a liberal guideline, and that most adults are in nitrogen balance with only about 0.6-0.7 g of protein per kilogram of body weight per day. This guideline pertained to average adults. What about very active persons, especially athletes during periods of intense training? During periods of intense exercise training, whole-body protein turnover is increased. This suggests a need for greater nitrogen intake. Furthermore, many athletes want to be in positive nitrogen balance, to gain mass (especially muscle). What are the dietary protein requirements in these cases?

The earliest research studies on this topic dealt with athletes training to increase muscle mass. This is not surprising since the aim of these athletes is to increase masses of tissues made up largely of proteins. In general, most of these athletes will ingest enough protein to be in positive nitrogen balance if they follow the old guideline of 1 g protein/kg body weight/day. To be on the safe side, however, many sports nutritionists recommend that athletes who are just starting intense weight training (e.g., novice body builders), in whom gains in mass are relatively fast, should take in 1.6-1.7 g protein/kg/day. They recommend that experienced lifters, in whom gains in mass are slower, should ingest 1.1-1.2 g/kg/day. More recently, studies have indicated that endurance athletes may need more dietary protein than the average person. The recommendation is that during intense endurance training, athletes ingest 1.2-1.4 g protein/kg/day.

 

 
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Carbohydrates, Fats and Proteins as Substrates for Aerobic Metabolism

Protein Use (cont.)

The next practical question is: Are athletes taking in enough protein? Most are. Studies have shown that most athletes in the United States take in 1.2-1.5 g protein/kg/day in their diets. Weight-training athletes often take in more. This suggests that dietary protein intake is not limiting for most athletes. A possible exception to this is the athlete who religiously avoids dietary fat. Dietary fat is often associated with proteins, so limiting fats may limit protein intake. Endurance athletes may be most susceptible, since they consciously try to keep weight down and they typically place great emphasis on carbohydrates in the diet.

Are dietary protein supplements beneficial for athletes? Psychologically, perhaps. If an athlete is convinced that he/she is doing better with the supplement, or conversely, is convinced he/she is doing worse without the supplement, then it may be worthwhile. But protein supplements probably have no physiological benefit. As discussed in the previous paragraph, few athletes need more protein than they ingest in the diet. If dietary protein intake is inadequate, of course supplements will help. But excess proteins beyond nutritional needs are converted to other substances, such as fat, or are simply metabolized for energy. The nitrogen excreted will increase to match the increased nitrogen taken in, to keep the person in nitrogen balance. Gaining muscle mass isn't as simple as taking in extra protein!

There are interesting questions about potential benefits of ingesting specific amino acids, since it is conceivable that diets could be deficient in certain amino acids. Furthermore, certain amino acids may play key regulatory roles in terms of anabolism, delaying fatigue, or the like. I am not aware of research that supports beneficial effects of ingesting larger amounts of specific amino acids (assuming one has a balanced protein intake and is not dietarily deficient). Perhaps future research will show this. In the meantime, I would remind you that marketing people do not have to back up claims with scientific evidence. Makers of supplements in general are more interested in athletes' money than in their physiology!

 

 
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Carbohydrates, Fats and Proteins as Substrates for Aerobic Metabolism (cont.)

Effect of Diet

One of the major challenges for the body in terms of aerobic metabolism is to use just the right mix of fats and carbohydrates. Using relatively more carbohydrates is advantageous because of the much higher power that can be generated using carbohydrates, and because more energy can be derived per unit of oxygen consumed. On the other hand, if exercise is prolonged and endurance is a factor, using carbohydrates at too high a rate could lead to depletion of carbohydrate stores before the end of the event. As we have seen, one of the most important considerations in this regard is the exercise intensity. Another is diet, both diet prior to competition and ingestion of fuel during competition.

 

 
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Carbohydrates, Fats and Proteins as Substrates for Aerobic Metabolism

Effect of Diet (cont.)

Precompetition Diet. There is abundant research evidence to support benefits of a high-carbohydrate diet for endurance athletes. Total body stores of carbohydrates are increased when on a high-carbohydrate diet (60-70% of total caloric intake from carbohydrates) compared with a low-carbohydrate (30-40% of calories from carbohydrates) or even a mixed diet (50-60% of calories from carbohydrates). And most of this increase is in the form of glycogen stored in skeletal muscles. Therefore, the athlete who is on a high-carbohydrate diet has an advantage during endurance performance; since he/she is starting the event with more stored glycogen, glycogen depletion is less likely.

Either separately or in addition to a regular diet that is high in carbohydrates, many athletes use a regimen of carbohydrate-loading for several days before competition. Carbohydrate-loading is also known as glycogen loading, carbohydrate or glycogen packing, and glycogen supercompensation. In one form, this involves simply eating a diet very high in carbohydrates for 2-3 days prior to competition. This increases muscle glycogen stores. A variation of this involves intense endurance exercise to lower muscle glycogen stores during the 4-6 days before competition, sometimes while eating a relatively low-carbohydrate diet. Then a very high-carbohydrate diet is eaten during the 2-3 days before competition. There is some evidence that the combination of initial depletion of muscle glycogen followed by a high-carbohydrate diet results in even higher muscle glycogen levels than the dietary maneuver by itself.

A word of caution is in order here. Changing diets and manipulating carbohydrate stores in the body can affect a lot of things, including how a person feels (and therefore psychological variables), body weight, and performance during training bouts. Regimens aimed at increasing muscle glycogen stores should be practiced before major competitive events. The athlete should be comfortable with and confident in the routine prior to competition.

 

 
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Carbohydrates, Fats and Proteins as Substrates for Aerobic Metabolism

Effect of Diet (cont.)

Whether an athlete uses a carbohydrate-loading regimen or not, he/she is well-advised to eat a regular diet that is high in carbohydrates. Besides the benefits of this related to the actual period of performance, this has another important benefit. A regular high-carbohydrate diet will decrease chances of depleting muscle glycogen during training bouts, and will make replenishment more rapid after training bouts. During periods of regular, intense training, muscles can become progressively depleted of glycogen. For example, consider an athlete who does intense endurance training bouts on 4-5 consecutive days. After the first day’s bout, muscle glycogen levels may not be total depleted, but they will be reduced. Let’s say concentration is 50% of the pre-bout value. Some replenishment then occurs before the second day’s training bout, but only to 80% of the original concentration. So, muscles are starting this bout partially depleted. At the end of this bout, concentration may be 35% of the original value. Then replenishment may be to only 70% of original concentration by the start of the third day’s training, etc. This progressive depletion of muscle glycogen is a critical consideration with regular, intense training. If it occurs, training will be impaired. Progressive depletion is less likely to occur when the athlete is on a high-carbohydrate diet. Also, of course, including days of lighter or other types of training every few days will allow time for restoration of glycogen stores.

 

 
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Carbohydrates, Fats and Proteins as Substrates for Aerobic Metabolism

Effect of Diet (cont.)

Ingesting Carbohydrates During Exercise. Ingesting carbohydrates during exercise can delay fatigue during prolonged exercise that might be limited by depletion of carbohydrate stores. The American College of Sports Medicine recommends that carbohydrates be ingested at a rate of 30-60 grams per hour during intense exercise that lasts longer than 1 hour (Med. Sci. Sports Exerc. 28:I-vii, 1996). The carbohydrates may be sugars (e.g., glucose, sucrose) or starch (e.g., maltodextrin). Ingesting carbohydrates during exercise does not seem to reduce rate of muscle glycogen use. Rather, it provides glucose to the blood and thereby spares liver glycogen. This prolongs the duration of exercise before liver glycogen would be depleted. Furthermore, it may allow skeletal muscles to use relatively more blood glucose late in exercise, when muscle glycogen stores are low.

 

 
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Review of Lesson

You have come to the end of the online content of Unit 2 - Lesson 2. When you want to review the concepts in this lesson, use the Learning Objectives on Page 1 of this lesson and the Review Questions below. These should be a good study guide. If you can correctly do what the Objectives and Review Questions ask, you will have mastered the most important concepts in this lesson. Please realize, however, that these do not exhaustively cover all the information in the lesson.  

If you are uncertain about any Objective or Review Question, or if you want clarification or expansion of any point in the lesson, I urge you to start a threaded conference discussion on WebBoard. Other students may have the same concerns, will probably benefit from the discussion, and may have the information you seek. And, of course, feel free to contact me (Dr. Eldridge) for assistance.

Be sure to check the Announcements Page to see whether there is a specific WebBoard or other assignment.

Review Questions

1. Analyze in semi-quantitative terms the contributions of the three ATP-formation methods to total power input in each of the following activities: (a) walking at a brisk pace for 20 minutes; (b) throwing a single fastball pitch in softball; (c) rowing as part of a crew of eight in a 2000-meter race (time = about 6 minutes); (d) cycling 20 miles in 44:56, a personal record. State the most likely limiting factor if the exercise would be limited by metabolism.

2. Among non-physiologists, one often hears something like the following: "Energy at the start of exercise comes from the CK reaction. After the CP is depleted, glycolysis kicks in and provides the energy for the next 1-2 minutes. This gives time for aerobic metabolism to kick in, and aerobic metabolism provides the energy after 2 minutes." Discuss the erroneous concepts in this quotation.

3. Select a person you know and estimate the total kilocalories of energy stored in that person in the form of carbohydrates and in the form of fats. Explain the bases of your estimates.

4. When a person is doing intense exercise that he/she could maintain for no more than 5-10 minutes, is it more advantageous for this person to use fats or to use carbohydrates as substrate for aerobic metabolism? Explain your answer.

5. State the "50-50-50 Rule of Thumb" related to carbohydrate and fat utilization during acute exercise.

6. One often hears that, "For burning fat, the best exercise is low-intensity exercise." Discuss what is true and what is false or at least misleading about this statement.

7. Calculate your recommended daily dietary protein requirement, and explain the basis of your estimate.

8. List three acute exercise regimens for which it might be advantageous to carbohydrate load, and three acute exercise regimens for which it might be advantageous to ingest carbohydrates during the exercise.

 
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You have reached the end of lesson 2.

 
 
Lesson: Lesson 3 4 Lesson 3 Edit this lesson (Lesson 3)
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Lesson 3 continues the specific study of energy metabolism during exercise, dealing with the role of lactic acid in exercise physiology, maintenance of blood glucose, and metabolic factors in the recovery from exercise.

Learning Objectives

After completion of Lesson 3, the student should be able to:

1. Define the following terms, and be able to use each term appropriately in discussions: lactate shuttle, lactate threshold, maximal lactate stead state, acidosis, hyperglycemia, hypoglycemia, gluconeogenesis, Cori Cycle, glucose-alanine cycle, oxygen debt, excess postexercise oxygen consumption.

2. List the substances to which lactic acid can be converted.

3. Describe the responses of blood lactic acid concentration to exercise of different intensities and durations. Relate these responses to the concepts of rate of appearance in the blood and rate of disappearance from the blood.

4. Discuss the relationship between exercise intensity and lactate threshold as it affects endurance performance.

5. Discuss the roles of the liver and skeletal muscles in blood glucose homeostasis under various conditions, including resting and acute exercise.

6. Discuss oxygen debt and excess postexercise oxygen consumption -- the terms themselves, the concept, and the causes of the oxygen debt or excess postexercise oxygen consumption.

Outline of Content

V.  Lactic Acid Metabolism

   A.  Introduction

   B.  Fates of lactic acid

   C.  Response of blood lactic acid concentration
         to exercise

      1.  Introduction

      2.  Lactate threshold (OBLA—Onset of Blood
            Lactate Accumulation)

      3.  Maximal lactate steady state

VI.  Maintenance of Blood Glucose

VII.  Recovery From Exercise  

 

 
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Lactic Acid Metabolism

We have already dealt with some important aspects of lactic acid metabolism. I hope you already appreciate that lactic acid formation is essential to anaerobic glycolysis, and that lactic acid still contains a lot of energy that can be used in metabolism. (If you don’t, I suggest you go back and review the earlier sections that dealt with this.) It is true that lactic acid accumulation in tissues can lead to problems, just like the accumulation of many acids would. In muscle tissue, increased acidity (acidosis) eventually impairs the ability of muscle to generate force and to provide energy for contraction. So, it is usually advantageous to minimize lactic acid accumulation in muscle, and to remove it as quickly as possible when it has accumulated. But lactic acid is not all bad. Lactic acid has many positive features. In this section we will review and highlight certain points about lactic acid metabolism.

 
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Lactic Acid Metabolism (cont.)

First I want to comment on the terms lactic acid and lactate. You will see both terms in exercise physiology literature.

What makes something an acid is its ability to donate a positively charged hydrogen ion when mixed with water. Whether the acid is a strong one or not depends on the number of hydrogen ions donated to the solution. It’s these hydrogen ions that are so reactive and make acids so corrosive. We could have a jar filled with hydrogen chloride crystals that are essentially harmless. But as soon as these crystals come into contact with water, very many hydrogen ions are released and we now have a solution of very corrosive hydrochloric acid. Lactic acid and lactate are identical 3-carbon molecules except for one thing: lactic acid still has the potentially acidic hydrogen attached, while lactate does not. In fact, lactate has a negative charge because it has lost the positive charge of the hydrogen ion. So, lactic acid is technically the acid form and lactate is the so-called “salt of the acid.” Both forms exist in the body, although normally there is more of the lactate form than the lactic acid form. When considering the physiology of acid-base regulation, distinguishing between the acid and the salt forms is critical. This is not so critical in terms of energy metabolism, because the two forms contain the same amount of energy and they are processed identically. So, in our discussions of metabolism, I will include both forms in the single term “lactic acid.”

 
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Lactic Acid Metabolism (cont.)

Fates of Lactic Acid

Lactic acid is formed in the last reaction of anaerobic glycolysis, an oxidation-reduction reaction in which pyruvic acid is converted to lactic acid. This can occur in any tissue in the body. The greatest potential for formation of lactic acid is in skeletal muscles during intense exercise. This is especially the case with muscle fibers that have little mitochondrial mass and therefore low capacities for aerobic metabolism. We will study the different types of skeletal muscle fibers later in the course. For now, however, I want to simplify and emphasize two different types of fibers, I and IIb. Type I fibers have a lot of mitochondria and low glycolytic capacity. Type IIb fibers are the opposite; they have high maximal rates of glycolysis and few mitochondria. Type I fibers do not generate much lactic acid; type IIb fibers do.

What happens to the lactic acid that is formed? Sooner or later, lactic acid is converted back to pyruvic acid. And pyruvic acid can be converted to many other compounds. Some of the important compounds to which pyruvic acid can be converted are:

(a) acetyl CoA, which can enter the Krebs Cycle and be a substrate for aerobic metabolism; acetyl CoA is also an important building block for forming many larger compounds in the body;

(b) glucose; this is done by essentially reversing glycolysis, and the process is known as gluconeogenesis;

(c) the amino acid alanine, through transamination reactions.

The basic point here is that the carbon atoms in lactic acid can potentially become part of almost any molecule in the body.

 

 
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Lactic Acid Metabolism

Fates of Lactic Acid (cont.)

Let’s examine an exercise situation to see what happens to most lactic acid that is formed. Most lactic acid will be formed in type IIb muscle fibers. Most of this lactic acid will be transported across the cell membrane of these fibers to the extracellular fluid, and most will enter the blood (some will enter type I muscle fibers adjacent to type IIb fibers). The tissues that are the major sites of removal of lactic acid from the blood are the liver, the heart, and type I skeletal muscle fibers. The heart and type I skeletal muscle fibers are well-equipped to use lactic acid as a substrate for aerobic metabolism. Therefore, these tissues take lactic acid from the blood, convert it to pyruvic acid and then to acetyl CoA for the Krebs Cycle. By doing this, these tissues simply substitute lactic acid for glucose or other substrates. Lactic acid that is taken out of the blood by the liver is converted to pyruvic acid, and then most is converted to glucose. This glucose can then be put into the blood and carried to any tissues in the body that may need it. Dr. George Brooks and his colleagues have coined the term lactate shuttle to refer to the function of lactic acid as a form of shuttling an energy substrate from one tissue to another throughout the body.

The energy remaining in a lactic acid molecule formed in one cell can in fact be transferred to and used by many other cells. This energy can be used in many ways, but the most common are:

  • for formation of ATP in aerobic metabolism (after conversion of lactic acid to pyruvic acid and then acetyl CoA) and 

  • for formation of glucose (via gluconeogenesis, predominantly in the liver). 

The fate of most lactic acid is to become a substrate for aerobic metabolism.

When does this shuttling of lactic acid among different tissues take place? The simple answer is, “all the time.” Even when we are resting, there is some lactic acid being formed somewhere in the body (though not much), but other tissues are using the lactic acid. This occurs to a greater extent during exercise and during recovery from exercise. Let’s look at this in more detail. 

    

 
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Lactic Acid Metabolism (cont.)

Response of Blood Lactic Acid Concentration to Exercise

The concentration of any substance in a tissue depends on how fast the substance is being added to the tissue compared with how fast the substance is being removed from the tissue. These two processes are referred to rate of appearance (Ra) and rate of disappearance (Rd), respectively. When Ra is the same as Rd, the concentration of the substance in the tissue stays constant. When Ra is greater than Rd, the concentration increases in the tissue, and when Rd is greater than Ra, the concentration decreases in the tissue.

This applies to the concentration of lactic acid (abbreviated [HLa]) in the blood, muscle, the liver, or any other tissue. When we observe, for example, that [HLa] has increased in the blood during intense exercise compared with the preexercise value, we know that Ra was greater than Rd during the time between the two measurements. Beyond that, we must be careful in interpreting the increased blood [HLa]. It is tempting to conclude that there must have been increased rate of anaerobic glycolysis with obligatory production of lactic acid, and this is probably true. But we can’t be sure. Other things occur during intense exercise that likely affect either the Ra or the Rd of lactic acid. For example, blood flow may be increased to tissues that are producing lactic acid; this facilitates the Ra of lactic acid in the blood. At the same time, blood flow to the liver may be decreased during intense exercise; this may decrease the Rd of lactic acid from the blood, because the liver is a major site of removal of lactic acid. So, we must be careful in trying to explain changes in [HLa] during and after exercise.  

 

 
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Lactic Acid Metabolism

Response of Blood Lactic Acid Concentration to Exercise (cont.)

One other point is very important: Remember that the type IIb skeletal muscle fibers are not very well equipped for aerobic metabolism, so they normally produce a lot of ATP by anaerobic glycolysis. Therefore, these fibers normally produce lactic acid, even when there is plenty of oxygen available. In contrast, the type I muscle fibers (and cardiac muscle) produce relatively little ATP by anaerobic glycolysis. In exercise of low intensity, few type IIb fibers are active. In intense exercise, type IIb fibers are recruited and become very active. As a result, there is going to be much more lactic acid formed during the intense exercise simply because more type IIb fibers are contracting. This is a function of the pattern of recruiting muscle fibers and may have absolutely nothing to do with oxygen availability.

Point of Emphasis: When oxygen supply to a tissue is less than needed, rate of glycolysis and lactic acid production will increase. But an increased rate of lactic acid production or increase in [HLa] does not necessarily mean that the oxygen supply to the tissue was inadequate; other things can cause these increases.

In this section I will emphasize two important concepts: the lactate threshold and the maximal lactate steady state.

 
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Response of Blood Lactic Acid Concentration to Exercise (cont.)

Lactate Threshold

There is some disagreement among exercise physiologists over terminology in this area, and there is also inconsistent use of terms in the literature. Three terms have been used most to refer to the same phenomenon: lactate threshold, anaerobic threshold, and OBLA (which stands for onset of blood lactate accumulation). Any of these is OK, although “anaerobic threshold” suggests an underlying mechanism that many do not understand and may misapply. I will use the term lactate threshold.

Lactate threshold is defined as the highest exercise intensity before arterial blood lactic acid concentration is increased above the resting level. This exercise intensity may be expressed in units of VO2, power output, walking or running speed, or the like.

Lactate threshold is usually determined with a continuous, progressive exercise test that starts at a very low intensity and gradually increases to higher and higher intensities. [HLa] in the blood (usually sampled from a fingertip) is measured at frequent intervals. An idealized response to such a test is illustrated in the figure. In this test, the subject pedaled a bicycle ergometer, starting at 25 watts and increasing 25 watts every 2 minutes. Blood was sampled near the end of each 2-minute stage for measurement of [HLa].

 
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Response of Blood Lactic Acid Concentration to Exercise

Lactate Threshold (cont.)

As illustrated in the figure on the previous page, a person can exercise at low intensities without [HLa] increasing in the blood. At a certain intensity, however, there will start to be elevated blood [HLa]. In the example in the figure, this initial elevation in [HLa] occurs at a power output of 125 watts. Therefore, the lactate threshold is 100 watts; this is “the highest exercise intensity before blood [HLa] is increased above the resting level.” Let’s assume that this person’s VO2max is 2.70 L/min, and the VO2 measured while working at 100 watts is 1.44 L/min. In this case, we could also say that this person’s lactate threshold is 1.44 L/min or 53% of VO2max. So, based on this test, “the highest exercise intensity before blood [HLa] is increased above the resting level” (i.e., lactate threshold) can be described as 100 watts, a VO2 of 1.44 L/min, or a VO2 of 53% of VO2max.

The most important point of application is that at all intensities above the lactate threshold, there will be some degree of acidosis. This will be minor at intensities just above the threshold, but it becomes more and more significant as exercise intensity gets higher and higher.

NOTE: Resting blood [HLa] is typically about 1.0 millimole per liter (mM). Because most tests for determination of the lactate threshold do not come out as nicely as the idealized curve in the figure, it is sometimes difficult to determine exactly where the increase above resting levels first occurs. Therefore, for practical reasons, some define the lactate threshold as “the exercise intensity at which blood [HLa] = 2 mM.” Although 2 mM is twice the normal resting level, this is still a very low [HLa]. Referring back to the figure, using this 2 mM criterion, we would define the person’s lactate threshold as just a little more than 150 watts.

 
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Response of Blood Lactic Acid Concentration to Exercise

Lactate Threshold (cont.)

The lactate threshold is typically 50-60% of VO2max in untrained persons, but 70-80% of VO2max in highly trained endurance athletes. The higher lactate threshold means that the endurance athlete can exercise at much higher intensities without lactic acidosis. Since acidosis can limit performance, this is another advantage of training: The trained athlete can exercise at higher intensities without the threat of limitation by acidosis.  

Example: Consider an untrained person (with lactate threshold = 50% VO2max) and an endurance athlete (with lactate threshold = 75% VO2max). If both run at 70% VO2max, the untrained person will have a blood [HLa] that is increased above resting but the trained person will not.  In this case, acidosis may eventually limit performance when the untrained person runs at this intensity, but not performance of the trained athlete at this intensity. (I hope you have noted than the endurance athlete would also have a higher VO2max that the untrained person. So, 70% of VO2max would be associated with a higher exercise intensity in the trained athlete. The athlete would be running at a faster pace and still would have lower blood [HLa].)

 
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Response of Blood Lactic Acid Concentration to Exercise (cont.)

Maximal Lactate Steady State

As a reminder, steady state refers to a state or condition in which some variable or set of variables is not changing over time. A lactate steady state refers to a condition in which the blood [HLa] remains constant over time. When we are resting, we are in a lactate steady state; the blood [HLa] may change a little from one minute to the next, but it stays very close to 1.0 mM. In some exercise, the blood [HLa] stays constant even if the exercise is continued for a long period of time. In fact, if we stop to think about it, a person could not run for 2, 3, 4 or more hours (e.g., the marathon) if blood [HLa] continued to increase. If this happened, acidosis would eventually lead to fatigue.  

Researchers have discovered that the highest blood [HLa] a person can typically have during exercise without it continuing to increase is about 4 mM. In other words, if during exercise the blood [HLa] increases to 5 mM (or more), the [HLa] will not stay at a steady state. Rather, it will continue to increase as long as the person tries to exercise at the same intensity. And eventually, acidosis will be a factor in limiting the duration of this exercise. In other words, a blood [HLa] of 4 mM is associated with a maximal lactate steady state (MLSS) – The condition in which the blood [HLa] is the highest it can be and still remain constant over time.

 
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Response of Blood Lactic Acid Concentration to Exercise

Maximal Lactate Steady State (cont.)

It is very important for the endurance athlete to know the exercise intensity associated with the maximal lactate steady state. This is the intensity for optimal performance of long-duration exercise in terms of considerations related to acidosis. Intensities less than this intensity would result in less-than-best performance. Intensities greater than this may lead to fatigue before completion of the event. This latter outcome depends on the total duration of the event and how high above the optimal intensity the athlete’s intensity is. For example, in the marathon, even the slightest rate of increase in blood [HLa] would eventually lead to problems over the 2+ hours of running. In this case, it is critical that the runner not run at a pace at which blood [HLa] increases to greater than 4 mM. In a race that lasts only 25-30 minutes (e.g., 10 km), the runner could probably run at a pace a little above the intensity associated with maximal lactate steady state. In this case, the blood [HLa] would continue to increase throughout the race, but the race would be over before the [HLa] became limiting (unless the pace was too fast!).

Of course a big part of the challenge for endurance athletes and their coaches is to find the optimal pace for running, swimming, or cycling a given distance. This can be done through trial and error. On the other hand, measurement of blood [HLa] during exercise at different paces can be very useful. Such measurements are not difficult and not extremely expensive. As a group, competitive swimmers have used blood [HLa] measurements a lot to guide their training and determine appropriate paces for different events.

 
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Maintenance of Blood Glucose

The normal concentration of glucose in the blood is 60-110 mg per 100 mL of blood (60-110 mg/dL). The total blood volume of a person of average body size is about 5,000 mL. Therefore, the average person has a total of 3,000-5,500 mg of glucose in the blood. Since there is about 4 kcal of energy stored in each gram of carbohydrate, the total amount of glucose in the blood represents about 12-22 kcal of energy. This is only about 1% of the total energy stored in carbohydrates in the body. As with any substance in the blood, the concentration of glucose (abbreviated [glucose]) in the blood depends on the difference between the rate of appearance (Ra) of glucose in the blood and the rate of disappearance (Rd) of glucose from the blood.

The glucose in the blood is being transported to various tissues for various uses. When the body is in an energy-storage mode, such as while resting after a meal (a postabsorptive state), glucose is taken out of the blood by certain tissues and used to store energy. One example of this is the uptake of glucose from the blood by skeletal muscles for storage as glycogen. A second example is the uptake of glucose from the blood by fat cells. This glucose is used in the formation of triglycerides for storage of fatty acids. The hormone insulin, produced in the pancreas, is essential for normal uptake of glucose by fat cells and by resting skeletal muscle fibers. When insulin levels are not high enough (as in diabetes) or when peripheral cells become resistant to insulin (as often occurs in obesity), cells do not take up glucose from the blood as they normally would, and blood glucose concentration increases above normal levels (hyperglycemia).

The most critical use of blood glucose is as substrate for energy by the brain. The brain has a relatively high rate of metabolism that stays fairly constant no matter what the body may be doing. Normally the brain uses glucose almost exclusively as the substrate for forming the ATP it needs. Brain function is obviously critical. Therefore, maintaining a supply of glucose to the brain via the blood is a very high priority for the body. When blood glucose concentration falls below about 60 mg/dL (hypoglycemia), a person will typically experience symptoms such as dizziness, lightheadedness, disorientation, or fainting, which relate to abnormal brain function.

 
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Maintenance of Blood Glucose (cont.)

During exercise, active skeletal muscle fibers take up glucose from the blood in proportion to the exercise intensity. The reason for this has been an intriguing question for exercise physiologists for a long time. Muscle fibers have their own glucose supply in the form of stored glycogen, they have stored triglycerides within the fibers, and they can take up a lot of fatty acids from the blood for energy metabolism. It seems that muscle fibers could get along fine without glucose from the blood, and that they would leave the blood glucose for the brain. This is not what happens, however. Most of the energy for ATP formation in skeletal muscle fibers is derived from stored glycogen and/or fatty acids, but skeletal muscles use some glucose taken up from the blood.

It is significant that skeletal muscle fibers need insulin for glucose uptake only when they are resting. Muscle contraction has an “insulin-like effect.” That is, muscle contraction by itself results in enhanced uptake of glucose by the fiber, so insulin is not needed for the contracting fiber to take up glucose. In fact, insulin levels in the blood normally fall during exercise. This is as expected, since skeletal muscle fibers do not need the insulin for glucose uptake when they are contracting, and fat cells break down triglycerides during exercise, rather than storing energy.

 
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Maintenance of Blood Glucose (cont.)

The liver has primary responsibility for maintaining an adequate supply of glucose for the blood to transport to the various tissues. In the postabsorptive state, glucose from digestion of carbohydrates is taken up by the blood in the gastrointestinal (GI) tract. The liver takes up some of this glucose and stores it as glycogen. The liver will normally store the equivalent of about 500-600 kcal of energy as glycogen. When several hours have passed since the last food has been eaten and the blood is no longer taking up glucose from the GI tract, this liver glycogen is the primary source of glucose for the blood. The liver then breaks down its stored glycogen to glucose and puts it out into the blood.

The liver can also make glucose from smaller precursor molecules by the process called gluconeogenesis (i.e., the formation of glucose from smaller substances, such as pyruvic acid; gluconeogenesis literally means “making of new glucose”). This glucose can also be put into the blood. Gluconeogenesis essentially involves reversing the reactions of glycolysis (with a few exceptions), making one glucose molecule from two pyruvic acid molecules. Where does the pyruvic acid come from?

 
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Maintenance of Blood Glucose (cont.)

There are two major sources of pyruvic acid for gluconeogenesis.

First, much of the pyruvic acid comes from skeletal muscle fibers. This can be directly or, especially, indirectly in the form of lactic acid formed by type IIb fibers. This lactic acid is transported via the blood to the liver, the liver converts it to pyruvic acid, converts the pyruvic acid to glucose, and puts the glucose into the blood. This sequence involving muscle, the liver, and the circulation in providing blood glucose from pyruvic acid and lactic acid formed in muscle fibers is known as the Cori Cycle.

The second potential source of pyruvic acid for gluconeogenesis in the liver is amino acids. Physiologists have hypothesized a number of different pathways by which pyruvic acid is formed from various amino acids. Probably the most significant is the glucose-alanine cycle involving skeletal muscle. This is thought to work as follows. The nitrogen-containing amino groups from various amino acids in skeletal muscle fibers (especially the branched chain amino acids) are transferred to pyruvic acid in transaminase reactions. This converts pyruvic acid to the amino acid alanine. (In the process, the original amino acids become available as substrate for aerobic metabolism.) This alanine is put out by the fiber into the blood and carried to the liver. In the liver, the alanine is converted back to pyruvic acid. Therefore, the glucose-alanine cycle is a way that amino acids from various proteins in the body can be used to provide glucose for the brain and other tissues. This sequence is especially important during prolonged fasting or starvation, when body carbohydrate stores have been depleted.  

 
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Maintenance of Blood Glucose (cont.)

I hope it is clear that skeletal muscle fibers can play a very important role in providing glucose either to other muscle fibers or to other tissues. Muscle fibers don’t do this directly – muscle fibers can’t put glucose from their stored glycogen directly into the blood, as the liver can. They do it indirectly by providing pyruvic acid and especially lactic acid (Cori Cycle), as well as alanine (glucose-alanine cycle) to the liver via the blood. The liver then uses these substrates in gluconeogenesis.  

 
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Maintenance of Blood Glucose (cont.)

Since the rate of using blood glucose increases during exercise (because skeletal muscles use more glucose from the blood during exercise), is hypoglycemia (low blood glucose concentration) a threat during exercise?

Hypoglycemia can occur during exercise, but it is likely to occur in only a couple of situations:

(a) If the amount of glycogen stored in the liver is low when the person starts exercising, the risk of depleting liver glycogen during the exercise is increased. In such a case, gluconeogenesis cannot keep up with the rate of blood glucose utilization. In other words, the Rd of glucose from the blood exceeds the Ra of glucose in the blood, so the glucose concentration falls. Remember that liver glycogen stores are built up primarily using glucose from the blood during the first few hours after eating. Therefore, when a person goes without eating for a prolonged period, liver glycogen is being used without being replenished. In fact, liver glycogen stores may be substantially reduced after a period of only 10-12 hours without carbohydrate intake. Risk of hypoglycemia with exercise is increased in this condition.

(b) Even if a person starts with a normal amount of glycogen stored in the liver, very prolonged exercise (i.e., 4-5 hours or longer of continuous or intermittent exercise) may deplete liver glycogen and result in hypoglycemia. Obviously, such exercise would have to be of low intensity or have many intervals of rest or decreased activity, so the average per-minute rate of glucose use would be low. But because the exercise duration is so long, the total amount of glucose used may be large. It is critical in exercise such as this to take in carbohydrates at regular intervals. This adds to the blood glucose and lowers the rate at which liver glycogen is used. The American College of Sports Medicine recommends ingesting 30-60 grams of carbohydrates per hour “during intense exercise lasting longer than 1 h.”

Except for these two cases, if a metabolic factor limits exercise performance, some other factor would limit the performance before depletion of liver glycogen and the resulting hypoglycemia.

 
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Recovery  From Exercise

There are many different aspects of recovery from exercise from the physiological perspective, to say nothing of psychological or other considerations. In this section we will focus on recovery of factors related to energy metabolism after exercise.

During exercise, especially if it is intense or prolonged, the demand for energy turnover is high. When the person stops exercising and “rests” (by comparison), the energy demand falls. But it doesn’t fall instantaneously to what it was before the exercise. Rather, it takes at least several minutes (and sometimes hours) for the energy demand to return to the preexercise level.

 
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Recovery  From Exercise (cont.)

ATP formation during recovery from exercise is essentially provided entirely by aerobic metabolism. As a result, oxygen consumption should accurately reflect the recovery metabolism. The figure depicts a typical time course of VO2 during and after a bout of exercise.  

 

As soon as a person stops exercising, VO2 drops rapidly over the first few minutes of recovery, and it may return completely to the preexercise level within the first few minutes if the exercise was not very intense or prolonged. After more intense or prolonged exercise, after the initial rapid decrease in VO2, there is a more gradual decrease in VO2 until the baseline level is reached. This oxygen consumed in exercise recovery above the baseline level represents an extra amount above what would normally be needed to support the activity of the recovery period (i.e., sitting, standing, slow walking, etc.).

 
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Recovery  From Exercise (cont.)

Physiologists in the early 1900s coined the term oxygen debt to refer to “the total volume of oxygen consumed after a bout of exercise above the preexercise baseline level.” The term is not a bad one, if the specific definition is recognized. But the term does imply that oxygen is borrowed during exercise and paid back during recovery, which is not strictly the case. Also, the term is badly misapplied by many non-physiologists. Therefore, the term “oxygen debt” should probably not be used. A term that has been suggested (and that I will use here) is excess postexercise oxygen consumption, abbreviated EPOC. The definition is the same as given earlier in this paragraph for oxygen debt. The rapid drop in VO2 in the first few minutes of recovery from exercise is referred to as the fast component of the EPOC, and the later, slower decrease in VO2 (when it occurs) is termed the slow component.

 

 
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Recovery  From Exercise (cont.)

Why must an extra amount of oxygen be consumed during recovery from exercise?

Let me propose an example: Let’s assume that we did an experiment in the laboratory in which a person was to run to exhaustion on the treadmill. Before the exercise, we measured the total volume of oxygen consumed by this person over a 10-minute period while he/she sat quietly in a chair. Then the person ran on the treadmill and was exhausted after 5 minutes of running. At exhaustion, the person sat in the chair again while we measured the volume of oxygen consumed during the first 10 minutes of recovery. (I’m only using this as an example. I’m not recommending this as a mode of recovery!) This person was doing the same thing (sitting in a chair) after the exercise as before. But we would have found that he/she consumed much more oxygen (e.g., 5 liters) during the 10 minutes of sitting after the exercise than during the 10 minutes before exercise. Why is this excess oxygen consumed after exercise?  

 
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Recovery  From Exercise (cont.)

A small part of the EPOC is simply oxygen to replace oxygen that had been attached to hemoglobin in the blood and myoglobin (a protein similar to hemoglobin) in muscle. Because of the relatively high rate of using oxygen during exercise, hemoglobin and myoglobin give up some of the attached oxygen. This is replaced quickly after exercise.

Most of the EPOC relates to extra oxygen consumed in the electron transport system to make ATP via aerobic metabolism. For one thing, more ATP is needed during recovery from exercise than before exercise. The major uses of this additional ATP are:

(a) replenishing the ATP supplies stored in muscle fibers; these stores are not large, and they may not be reduced much during exercise, but they still must be restored;

(b) replenishment of the CP used by active muscles during exercise; CP is formed by reversing the CK reaction:  ATP + C Þ ADP + CP;

(c) providing ATP for the additional energy required by the heart and the muscles of breathing, until these return to baseline states;

(d) gluconeogenesis, which is an anabolic process and requires energy; this particularly involves conversion of some of the accumulated lactic acid (perhaps 20% of the total) to glucose;

(e) replenishment of muscle and liver glycogen stores, which also is anabolic.  

 
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Recovery  From Exercise (cont.)

Which of these uses of additional ATP are completed quickly in recovery and which take longer?

The ATP and CP stores in muscles are replenished very quickly, certainly within a few minutes. This is why a person can do a series of many bouts of high power exercise, as long as he/she has brief recovery periods between bouts.

Work of the heart and breathing may be increased for 5-10 minutes or even longer, and the extra ATP to support these must be provided over that time period. (Monitoring recovery heart rate is a pretty good indicator of the heart’s work.)

Gluconeogenesis and especially glycogen synthesis are relatively slow processes. Still, it is rare for blood [HLa] to stay elevated above resting levels for more than 30 minutes after exercise. This suggests that excess lactic acid formed in glycolysis during exercise has been either converted to glucose or used as substrate for aerobic metabolism during this time period. Most of this lactic acid (probably 75-80%) is used as substrate for aerobic metabolism, and this simply replaces other fuels (e.g., glucose or fatty acids) that would have been used to generate ATP via aerobic metabolism.

I want to make a related point of application: For the most rapid removal of lactic acid after exercise, doing light exercise during recovery is best. This does two favorable things: (a) It keeps the blood circulation elevated, which facilitates the transport of lactic acid from tissues where it had accumulated during exercise to tissues that will metabolize it. (b) The light exercise keeps the demand for ATP elevated compared to a no-exercise recovery in muscle fibers with high aerobic capacity. As a result, lactic acid will be used as a substrate for aerobic metabolism at a higher rate to meet this increased ATP demand.

Glycogen synthesis takes hours and sometimes days before stores are replenished to preexercise levels. How long this takes depends on the degree of depletion of glycogen in the liver and especially in skeletal muscles (which depends on the intensity and duration of the exercise), and on the postexercise diet. Glycogen replenishment is most rapid during the first 6-8 hours after exercise, if carbohydrates are ingested. Even so, it typically takes 24-48 hours to totally replenish glycogen stores after exercise such as a marathon race, even with high carbohydrate ingestion. The demand for ATP from aerobic metabolism will be increased as long as glycogen synthesis is taking place. The extra VO2 associated with this would be spread over a long time period, so the per-minute rate would be very low. Therefore, it would be very difficult to measure this extra VO2 as part of the EPOC. In other words, the resting metabolic rate may be elevated for a day or two after certain acute bouts of exercise, but this elevation would likely be slight and very difficult to detect with standard measurement techniques.

 

 
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Recovery  From Exercise (cont.)

There is one other category of exercise-induced changes that contributes to the EPOC.  These are changes that loosen the coupling of the oxidation-reduction reactions to the phosphorylation of ADP in the electron transport system. This makes oxidative phosphorylation less efficient – more oxygen must be consumed to form a given amount of ATP.

For example, elevated muscle temperature and increased concentrations of the sympathetic hormones epinephrine and norepinephrine may loosen the coupling of oxidation and phosphorylation. Since elevations of these variables are common after exercise, these may contribute to the EPOC until these variables return to preexercise values.  

 
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Recovery  From Exercise (cont.)

In summary, as a result of the various stresses during exercise, many variables are changed in the body after an acute bout of exercise compared to the preexercise state. Many of these changes require oxygen use to restore the body to the preexercise state. This results in the consumption of an extra amount of oxygen for at least several minutes after exercise, the EPOC. Much of the EPOC relates to increased ATP formation to meet the extra energy demands of certain recovery processes. This increased ATP is formed in aerobic metabolism. Therefore, the ability to quickly make ATP via aerobic metabolism is important for recovery from exercise. So, even if aerobic metabolism contributes very little energy for ATP formation during exercise (such as during very high-power exercise that is completed in about 20-30 seconds), it is critical during the recovery. The athlete that can recover more rapidly has an advantage during performance involving intermittent bouts of high-power movements (e.g., basketball, soccer).

 
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Review of Lesson

You have come to the end of the online content of Unit 2 - Lesson 3. When you want to review the concepts in this lesson, use the Learning Objectives on Page 1 of this lesson and the Review Questions below. These should be a good study guide. If you can correctly do what the Objectives and Review Questions ask, you will have mastered the most important concepts in this lesson. Please realize, however, that these do not exhaustively cover all the information in the lesson.  

If you are uncertain about any Objective or Review Question, or if you want clarification or expansion of any point in the lesson, I urge you to start a threaded conference discussion on WebBoard. Other students may have the same concerns, will probably benefit from the discussion, and may have the information you seek. And, of course, feel free to contact me (Dr. Eldridge) for assistance.

Be sure to check the Announcements Page to see whether there is a specific WebBoard or other assignment.

Review Questions

1. Discuss the apparent paradox of lactic acid being both essential for anaerobic glycolysis and limiting.

2. Discuss the "insulin-like effect" of skeletal muscle contractions. What is it? What is its physiological and practical significance?

3. Discuss the role of skeletal muscles in providing glucose to other tissues -- at rest, during fasting or starvation; during an acute bout of exercise.

4. List three specific examples of situations in which hypoglycemia may be a threat.

5. List three specific examples of exercise activities in which lactic acidosis is a threat.

6. During a speed-skating race in the Calgary Olympics, I heard an "expert commentator" say about one of the skaters, "He's going into oxygen debt now." Analyze this statement from the physiological perspective.

 

 
 
Lesson: Lesson 4 5 Lesson 4 Edit this lesson (Lesson 4)
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Most of Lesson 4 deals with the important topic of changes in exercise metabolism resulting from training. A brief overview of how metabolism is regulated is also presented. The last several pages deal with appropriate use of specific terminology.

Learning Objectives

After completion of Lesson 4, the student should be able to:

1.  Describe the two major potential goals of training in terms of metabolism.

2.  Identify the changes that must take place in each of the three ATP-formation methods if (a) maximal power and (b) fatigue-resistance are to change.

3.  Discuss the specific effects of increased mitochondrial mass in trained skeletal muscles on endurance performance.  

4.  Discuss how training-induced changes in aerobic metabolism interact with anaerobic metabolism during exercise.

5.  Discuss general mechanisms by which metabolism is controlled.

6.  Define the following terms and be able to use each term appropriately in discussions: aerobic, anaerobic, aerobic metabolism, anaerobic metabolism, aerobic exercise, anaerobic exercise. Distinguish between common meanings and uses of these terms in different settings.

Outline of Content

VIII.  Effect of Training on Energy Metabolism

IX.  Regulation of Energy Metabolism

X.  Use of the Terms Aerobic and Anaerobic  

 

 
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Effect of Training on Energy Metabolism

Training may have two major goals in terms of metabolism:

Training Goal 1. To increase maximal power input, that is, the maximal rate of turning over energy for ATP formation. This in turn increases the maximal power output (assuming efficiency stays the same). This is obviously of great importance with performance involving maximal effort, but it has implications for submaximal exercise too.

Training Goal 2. To increase resistance to fatigue; in other words, to increase endurance at a given power.

In specific cases, training may have only one of these goals, but often training has both goals.

With these goals in mind, let’s study how training may affect each of the three methods for forming ATP.

 

 
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Effect of Training on Energy Metabolism (cont.)

To increase the maximal power of the CK reaction, the maximal activity of the enzyme CK must be increased. The most likely way for this to be accomplished is to increase the amount of CK in muscle fibers, that is, to synthesize more CK proteins. Increased maximal power of the CK reaction would allow an athlete to do very high-power exercise at even greater power. Manifestations of this training effect would include running at faster speeds over 5- to 20-second periods, such as, running bases at faster speeds in softball or baseball, competing in the 100 meters in track, and the like.

To increase endurance or fatigue resistance of the CK reaction, the concentration of CP in muscle fibers must be increased. Recall that the total amount of energy that can be transferred to ATP in the CK reaction is limited by the amount of CP available. When CP is depleted, no more ATP can be formed by the CK reaction. Therefore, increasing the normal pre-exercise concentration of CP in muscle fibers increases the total amount of ATP that can be formed by the CK reaction. Manifestations of increased endurance of the CK reaction would include ability to maintain a sprint speed for a longer time, such as, scoring from first base on a hit in softball or baseball without speed decreasing between third base and home plate, maintaining speed in the last 50 meters of a 200-meter dash, and the like.

 
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Effect of Training on Energy Metabolism (cont.)

To increase the maximal power of anaerobic glycolysis, the maximal activities of the enzymes of glycolysis must be increased. This applies especially to certain key rate-limiting enzymes. This most likely is accomplished by increasing concentrations of these enzymes in muscle fibers, that is, synthesizing more of these specific proteins. Manifestations of increased maximal power of anaerobic glycolysis would include faster speeds of running, swimming, and cycling over periods of 30 seconds to 2 or 3 minutes.

The total amount of energy that can be transferred to ATP in anaerobic glycolysis is limited by accumulation of lactic acid and the resulting acidosis. To increase this maximal capacity for ATP formation, muscle fibers must become more “tolerant” of lactic acid. This is accomplished with appropriate training by increasing the ability of muscle fibers to buffer lactic acid. Buffers remove hydrogen ions from solution, so they don’t lead to acidosis. Buffering ability is improved in trained muscle fibers. As a result, these fibers can produce more lactic acid before a given degree of acidosis occurs. More lactic acid production means more ATP formed in anaerobic glycolysis. There is also evidence that appropriately trained individuals can tolerate a greater degree of acidosis than untrained individuals can. Whether this results from a central nervous system adaptation or from actual changes in muscle tissues is not known. But if this occurs, this also increases the total capacity of anaerobic glycolysis for ATP formation. Similar to the examples given above for increased endurance of the CK reaction, increased endurance of anaerobic glycolysis would manifest itself in improved ability to maintain velocity of running, swimming, and cycling, in this case over periods of about 30 seconds to about 3 or 4 minutes.

 
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Effect of Training on Energy Metabolism (cont.)

Changes in aerobic metabolism with training are more complex than the changes in the anaerobic mechanisms. This is because changes in aerobic metabolism depend both on changes within muscle fibers and on changes in the oxygen transport system (especially the cardiovascular system).  In fact, a current point of debate among exercise physiologists is whether aerobic metabolism is limited more by “peripheral factors” (i.e., factors within muscle tissue) or by “central factors” (i.e., factors related to supplying oxygen to the peripheral tissues via the blood). It is likely that some individuals are limited by central factors and others by peripheral factors. If so, the challenge is to determine the limiting factors for a given individual, especially for athletes, so training can be designed to reduce the limitations. In this section I will focus on the changes that take place in muscle fibers with appropriate training. Changes in the central circulation will be addressed in the lessons on the cardiovascular system.

 
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Effect of Training on Energy Metabolism (cont.)

With appropriate training, there is an increase in mitochondrial mass in skeletal muscle fibers. There may be a doubling of mitochondrial mass in initially untrained muscle fibers after a period of training, a huge increase. The increase in mitochondrial mass includes increased amounts of the enzymes of the electron transport system, the Krebs Cycle, and beta oxidation. This has two physiologically significant results.

One result is that the maximal rate of generating ATP via aerobic metabolism (maximal aerobic power) is increased, but only if the oxygen transport system can provide the additional oxygen to support the increased aerobic metabolism. Since oxygen use is required in the last reaction of the electron transport system, the faster the rate of phosphorylating ADP in the electron transport system, the faster the rate of oxygen consumption. Therefore oxygen must be supplied at a faster rate to the mitochondria. Often this rate of supplying oxygen to muscle fibers increases with training along with the increases in mitochondrial mass. But if this supply does not keep up with the increase in mitochondrial mass, then the additional increase in mitochondrial mass no longer increases the maximal rate of forming ATP by aerobic metabolism.

 
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Effect of Training on Energy Metabolism (cont.)

The second result of the increase in mitochondrial mass with training is a carbohydrate-sparing effect. This occurs whether there is an increase in oxygen transport capacity or not. Trained muscle fibers with the increased mitochondrial mass are much better able to metabolize fatty acids. As a result, at a given rate of work, the trained person will use less carbohydrate and more fat as substrate for aerobic metabolism.

 

 

This in turn has another important effect: Lower rate of lactic acid formation. At a given rate of work above the original lactate threshold, the concentration of lactic acid in muscle fibers and in the blood is lower after training. This means reduced acidosis at given exercise intensities after training, and therefore less likelihood that acidosis will limit performance.

 

 

 
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 Effect of Training on Energy Metabolism (cont.)

The beneficial changes in aerobic metabolism with training are obvious in performances of long-duration events, such as running a marathon. Obviously, marathon running time is decreased with appropriate training. What physiological changes affect this?

After training, the runner has a higher maximal aerobic power. Therefore, running at a given percent of maximal aerobic power (e.g., 70%) occurs at a faster running speed. For example, a certain runner had a VO2max of 72 ml/kg/min, representing whole-body maximal aerobic power. Running at 70% of VO2max (i.e., VO2 = 50.4 ml/kg/min), he could run at an 8.7-mph pace and complete the marathon in 3 hours. This certainly does not represent an “untrained person,” but let’s assume that this runner had not trained hard for marathon running. So, after a period of intense training, this runner’s VO2max has increased to 78 ml/kg/min. Now 70% of VO2max is 54.6 ml/kg/min, allowing the runner to run at a 9.5-mph pace—a 2:45 marathon. These pre- and post-training data are summarized in the Table below.


  Pretraining Post-Training

VO2max
72.0 ml/kg/min 78.0 ml/kg/min
70% VO2max
50.4 ml/kg/min 54.6 ml/kg/min
Running Pace at 70% VO2max 8.7 mph 9.5 mph
Marathon Time 3:00 2:45

In actuality, VO2max may not increase a large amount with aerobic training. Many studies have suggested that increases in VO2max may be limited to 20-30% of the starting value, and that VO2max values reach a plateau relatively quickly with training (perhaps in months). Some questions remain on this issue, but two things seem certain:

(a) There is a large genetic component to maximal aerobic power and VO2max, probably at least 25% determined by genes. So athletes with very high VO2max values started with a high genetic potential. It is probably impossible for an untrained person with VO2max of 40 ml/kg/min to increase by 100% to 80 ml/kg/min with training to be able to compete in world-class endurance events.

(b) Even after VO2max has plateaued in trained athletes, endurance performance can still improve with training.

 
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Effect of Training on Energy Metabolism (cont.)

Let’s examine improvements with training apart from increased maximal aerobic power. And let’s continue to use the marathon as an example. Even if VO2max does not improve during a period of training, other physiological changes often occur, as noted earlier. These include increased lactate threshold, higher VO2 at maximal lactate steady state, and greater use of fat and less use of carbohydrate at given running speeds.

Let’s go back to the example of the runner we just used. In his “relatively untrained” state, his VO2max was 72 ml/kg/min, and his best marathon time was 3:00 (8.7-mph pace), running at 70% of his VO2max (50.4 ml/kg/min). One reason this pace was his best is that 50.4 ml/kg/min was associated with his maximal lactate steady state. In other words, when he would run at a faster pace than 8.7 mph and higher VO2 than 50.4 ml/kg/min, his muscle and blood lactic acid concentrations would continue to increase, leading to more and more acidosis. Also, even with glycogen loading, his muscles were almost depleted of glycogen at the end of the 3-hour marathon. Running at a faster pace would have depleted the muscle glycogen before finishing the race.

As a result of the changes with training, this runner could run at a faster pace (e.g., 9.0 mph, a 2:55 marathon) without continuous increase in lactic acid concentrations and problems with acidosis. This is true even though the faster pace would require higher VO2: for example, 51.8 ml/kg/min, 72% of his unchanged VO2max. Furthermore, at this faster pace, even with the higher VO2, rate of carbohydrate use would be no greater than it was before the training, and it may actually be lower. For example, at 8.7 mph before training, the proportions of substrates for aerobic metabolism may have been 70% carbohydrate and 30% fat (ignoring the small amount of protein use). After training, at the faster 9.0-mph pace, these percentages may have been 67% carbohydrate and 33% fat. As a result, the runner could run at the faster pace after training without being limited by muscle glycogen depletion before the end of the marathon, as he would have been at this pace before training.

 
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Effect of Training on Energy Metabolism (cont.)

To summarize, relatively long-duration endurance performance may be improved with appropriate training as a result of:

(a) increased maximal aerobic power (VO2max), although there seems to be a limit to this increase that is reached relatively early in training;

(b) reduced lactic acid accumulation; and/or

(c) decreased use of glycogen as substrate.

 
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Effect of Training on Energy Metabolism (cont.)

The changes in aerobic metabolism with training are easy to see in a long-duration event such as the marathon. Are these changes beneficial in shorter events?

Certainly there are some short-duration events that are impacted little, if any, by improved aerobic metabolism. To use a rather extreme example, changes in aerobic metabolism would not determine whether a sprinter could run 100 meters in 10.0 or 9.9 seconds.

What about the 1-mile run?

Is a high maximal aerobic power (VO2max) important, or even essential? And would increasing VO2max help lower the mile time from 4:00 to 3:50? Do other training-induced changes in aerobic metabolism improve performance in the mile run?

The answer to all three questions is YES. Let’s examine this further.

 

 
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Effect of Training on Energy Metabolism (cont.)

Many people can run at 15 mph, the average pace required to run a mile in 4:00. But very few people can run at 15 mph for 4 minutes. Why not? What is the limiting factor?

The limitation has to do with anaerobic metabolism. For most people, running at 15 mph requires a large input of energy from anaerobic glycolysis, with the resultant rapid production of lactic acid. Therefore, acidosis becomes severe before 4 minutes (in my case, way before 4:00!), so the 15-mph pace cannot be continued. What does aerobic metabolism have to do with this? In any exercise bout longer than about 2 minutes, more than 50% of the energy for ATP replenishment during the exercise comes from aerobic metabolism. So the 4-minute mile is more dependent on aerobic metabolism than anaerobic metabolism. But there is still a sizable contribution from anaerobic metabolism, which is the limiting factor. If this anaerobic contribution can be reduced, it becomes less limiting and the pace can be increased. There are two ways the anaerobic contribution can be reduced as a result of changes in aerobic metabolism.

 
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Effect of Training on Energy Metabolism (cont.)

One way the anaerobic contribution is reduced is by changes in maximal aerobic power (VO2max). Running at 15 mph requires oxygen at the rate of about 84 ml/kg/min. A few elite runners have VO2max values of 84 or higher. These runners could run the final 2 minutes or so of a 4-minute mile theoretically providing 100% of the ATP via aerobic metabolism. Anyone with a VO2max lower than 84 ml/kg/min (which includes some 4-minute milers) would still require ATP from anaerobic glycolysis during the last 2 minutes or so of the mile run, even after VO2 had adjusted to maximum. A person with a relatively low VO2max would require much more ATP from anaerobic glycolysis during the last 2 minutes than a person with a higher VO2max. So, increasing VO2max via appropriate training would lessen the anaerobic contribution during the last 2 minutes or so, and thereby lessen the chances of acidosis limiting the performance. This is illustrated in the figure below. Note the reduced amount of anaerobic metabolism, especially in the last 2 minutes of the race, as a result of the training-induced increase in VO2max.

 
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Effect of Training on Energy Metabolism (cont.)

There is a second way that anaerobic contribution to energy turnover during a mile run can be reduced as a result of changes in aerobic metabolism:

Appropriate training increases the rate of response of aerobic metabolism and VO2 at the start of exercise. This is sometimes referred to as oxygen on-kinetics, that is, the rate at which the system “turns on.” As a general rule-of-thumb, I have used 2 minutes as the time required after the start of exercise for aerobic metabolism to adjust to the increased demand. (Remember that the rate of energy turnover in aerobic metabolism starts to increase the instant the exercise starts, but it adjusts relatively slowly.) Appropriate training increases the rate of response of aerobic metabolism. For example, peak power input from aerobic metabolism may be reached by 1:50 after the exercise starts, rather than 2:00. This reduces the requirement for anaerobic metabolism in the early part of the exercise, while aerobic metabolism is adjusting. The figure below illustrates this concept. The only difference between the pre- and post-training situations is in how quickly VO2 adjusts after the start of exercise. The figure shows VO2max reached by 1:30 as a result of training, exaggerating the response to emphasize the point. Note the reduced requirement for anaerobic metabolism as a result of this more rapid response.

The total power input would be the same in the first second as in the last second of a 4-minute (or 3:50 etc.) mile run (assuming, for simplicity, an absolutely constant pace and no time for acceleration at the start; this could actually be done on a treadmill). So whatever power is not provided by aerobic metabolism IS provided by anaerobic metabolism. Lessening this anaerobic contribution lessens the acidosis, making it less limiting.

 

 
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Effect of Training on Energy Metabolism (cont.)

In summary, aerobic metabolism plays a huge role in running a mile, even though lactic acidosis due to a high rate of anaerobic glycolysis is the likely limiting factor. The higher the VO2max (maximal aerobic power), the less the anaerobic contribution, particularly during the last 2 minutes or so of the run. Elite milers as a group do not have the highest VO2max values in the world, but the values are high. A high VO2max is essential for running a mile in 4:00, or 3:50. In addition, the faster the rate of response of aerobic metabolism at the start, the less the anaerobic contribution during the first part of the run. Appropriate training can cause these improvements in VO2max and oxygen on-kinetics. Therefore, such training can definitely improve mile-run time.

Incidentally, elite milers have also developed through training a greater ability to buffer and tolerate lactic acid. This allows them to run at a faster pace with a greater contribution to total power input by anaerobic glycolysis but with less limitation by acidosis.

 
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Effect of Training on Energy Metabolism (cont.)

I have been using the nonspecific term “appropriate training” in discussions above. Probably the most important concern for the athlete and coach is, “Exactly what is appropriate training?”

Let me start the answer to this question with a reminder of two very important principles of training: the Overload Principle and the Principle of Specificity. These principles suggest that functioning of metabolic systems will improve only if they are stressed beyond what they are used to (i.e., overloaded), and only the systems specifically stressed in training will improve.

Let’s examine maximal power first. To increase the maximal power of a given method for replenishing ATP, exercise must be done that requires the maximal or near-maximal rate of energy turnover by that method.

 
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Effect of Training on Energy Metabolism (cont.)

The highest rate of energy turnover by the CK reaction occurs during very high power exercise that can be sustained for only about 5-20 seconds. Therefore, this type of exercise must be done in training to stimulate improvement in the maximal power of the CK reaction.

The highest rate of energy turnover by anaerobic glycolysis occurs during high to very high power exercise that can be sustained for only about 15-60 seconds. Therefore, this is the exercise that must be done in training to stimulate improvement in the maximal power of anaerobic glycolysis.

The highest rate of energy turnover by aerobic metabolism occurs during moderate to high power exercise that can be sustained for a maximum of about 1.5-3 minutes. Therefore, this exercise must be done in training to stimulate improvement in the maximal power of aerobic metabolism.

 

 
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Effect of Training on Energy Metabolism (cont.)

Note that each of these types of training involves relatively high power inputs (and outputs), and therefore none can be continued for very long. I hope this makes sense to you. Remember that we are dealing with improvement in the maximal rate of energy turnover. Therefore, the training principles require that the exercise intensities be high, to require high rates of the systems during the exercise. Because this training requires high power, it has to be done as interval training, that is, bouts of high-intensity exercise alternating with intervals of rest or light exercise.

 
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Effect of Training on Energy Metabolism (cont.)

Now let’s study fatigue resistance of each metabolic system. This is determined by the total amount of ATP the system can form in a single exercise bout (i.e., its capacity for ATP formation). As a general principle, to improve this capacity for ATP formation and, therefore, endurance of a system, training exercise must be done that requires a high total amount of ATP formation for that system.

Let’s look at aerobic metabolism first, because this has been researched most and the answer is pretty well known. Increasing maximal aerobic power also imparts increased fatigue-resistance in exercise involving long durations (e.g., 20 minutes – 3 hours). So training to improve maximal aerobic power will also improve endurance at a given power output. But performance in endurance events is improved also via training bouts at less than 100% of maximal aerobic power. For example, long bouts at 60-80% of maximum will increase mitochondrial mass in muscles and increase the ratio of fat-to-carbohydrate used as substrate during endurance events.

The most effective training for improving fatigue resistance of the CK reaction and anaerobic glycolysis is less well established, but probably it is similar to the interval training that results in increased maximal power of each of these systems. In general, the total energy turned over by the system during the entire training session is of more importance for developing endurance than is the power in any given training bout. Power during each “endurance-training” bout should be high, but it need not stress the system to maximum. And more bouts should be done.

 

 
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Effect of Training on Energy Metabolism (cont.)

In summary:

To increase maximal power of a system, training must include exercise in which the rate of energy turnover during the exercise is at or close to the system’s maximal rate; that is, the system is at or close to its maximal power.

To increase fatigue-resistance of a system, training must include exercise in which the system must turn over a relatively large total amount of energy; that is, the capacity of the system is challenged. The rate of energy turnover during this training need not be maximal power for the system.

 
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Effect of Training on Energy Metabolism (cont.)

Let me make a few final points about training and metabolism:

Point #1: The specific suggestions I have given for appropriate training to improve each ATP replenishment system are guidelines rather than exact laws. Furthermore, there is overlap in terms of training benefits. Two of the three methods for forming ATP can be trained fairly well with the same training regimen, although one regimen will not be optimal for both methods. It is not possible to provide significant training benefit for all three metabolic systems with a single training regimen.

An example: A track athlete does interval training. Each work bout is a 1-minute run that is near maximal effort. Each rest interval consists of 1-minute of very slow jogging. A total of 10 work-rest bouts are done in the training session. Which method of ATP formation benefits most from this? This exercise stresses anaerobic glycolysis most. Glycolysis must turn over energy at or near its maximal rate in each bout. This exercise provides considerable stress for aerobic metabolism also. The total power demanded exceeds aerobic power, so aerobic power will increase substantially and rapidly. It is true that the exercise is too short for aerobic metabolism to adjust completely, but there will still be a large increase in aerobic power during the 1-minute exercise. The CK reaction contributes power at the start of each exercise bout, but the total power is not close to the maximal power of the CK reaction. Therefore, there is little overload stress for the CK reaction. So, this interval training session benefits anaerobic glycolysis most, aerobic metabolism some, and the CK reaction little.

 

 
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Effect of Training on Energy Metabolism (cont.)

Point #2: This point is hopefully obvious, but I want to include it, just to be sure. In all of the examples given above regarding training, the training exercise must be done by the muscles that one wants to improve in terms of energy turnover (part of the Principle of Specificity). Thus, a sprinter must train especially the muscles that act at the hip, knee and ankle. And a boxer must include training of the muscles of the arms and shoulders.

Point #3: One aspect of training that indirectly affects metabolism relates to mechanics of movement. Specifically, if unnecessary movements can be eliminated or at least reduced, more of the power input can go toward the essential movements and performance will be improved. This relates to metabolism, but it is not an effect of training on metabolism per se. Therefore, I have not dealt with this aspect of training here, though I recognize and you should recognize how important it is.

 
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Regulation of Metabolism

Regulation of the chemical reactions of energy metabolism is extremely complex. Obviously, it is very important. Considering that the CK reaction can turn over energy at rates ranging from 0 kcal/sec to about 1 kcal/sec, anaerobic glycolysis from 0 kcal/sec to about 0.5 kcal/sec, and aerobic metabolism from almost 0 kcal/sec to about 0.25 kcal/sec, and that these systems must work together in a coordinated manner, extensive control is required. This doesn’t happen by chance. Details of this regulation are beyond the scope of this course. Nevertheless, I want to present an overview.

 

 
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Regulation of Metabolism (cont.)

There are several different types of control of the chemical reactions of the metabolic pathways. For example, reactions are controlled in a very simple and direct way by the amount of available substrate. Let me give a couple of examples.

One example we have already discussed is the availability, or lack of availability, of glycogen. If a muscle fiber’s glycogen concentration is zero, reactions that depend on glycogen cannot take place. The opposite is not the case, however. Just because the glycogen concentration is high in a muscle fiber does not mean that reactions that use glycogen go faster.

Another example we have discussed is the reaction in which pyruvic acid is converted to lactic acid, the last reaction of anaerobic glycolysis. One factor that determines the rate of this reaction is simply the amount of pyruvic acid present. The more pyruvic acid, the more lactic acid that is formed. Even though this is the case, this reaction is regulated by other mechanisms too.

Regulation of reactions based on depletion of substrate is a very primitive form of regulation.

 
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Regulation of Metabolism (cont.)

By far the most important mechanism for regulating energy metabolism is via regulation of enzymes. Enzymes exert major control over the reactions of metabolism, and many enzymes can be regulated themselves. In other words, they can be stimulated or inhibited by other substances.

For example, isocitrate dehydrogenase is the enzyme that converts isocitric acid to alpha-ketoglutaric acid in the Krebs Cycle. This enzyme is stimulated by ADP and inhibited by ATP. Therefore, if all other conditions are held constant, isocitric acid is converted to alpha-ketoglutaric acid at a faster rate when the concentration of ADP is high, and at a slower rate when the concentration of ATP is low. (The concept is the important thing with this example, not the specifics.)

 

 
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Regulation of Metabolism (cont.)

Many enzymes are regulated by substrates and products of the reactions of metabolic pathways. Others are regulated by the concentration of calcium in the cytoplasm (myoplasm) of muscle fibers. We will study the critical role of calcium in controlling muscle contraction in a later unit. For now, the important point is that calcium concentration rises to cause muscle contraction, and that same increase in calcium stimulates enzymes to speed up ATP production. So, calcium causes both the contraction that leads to increased need for ATP and increased supply of ATP – a very nice system.

Some enzymes are also regulated by hormones. Most hormones are chemical substances produced at one place in the body (in endocrine glands) and carried in the blood to another site to exert their effects. The endocrine system provides for a total-body control mechanism. The sympathetic hormones, such as epinephrine (adrenalin), for example, are important in the regulation of metabolism. Sympathetic hormones have effects on many different tissues in the body, generally preparing the body to respond to a stressor. One such stressor is exercise, and one of the effects of sympathetic hormones is to increase metabolic turnover of energy. And one of the ways these hormones do this is by stimulating certain enzymes. For example, epinephrine stimulates glycogen phosphorylase, the enzyme that catalyzes breakdown of glycogen to make glucose available for glycolysis.

 

 
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Regulation of Metabolism (cont.)

The primary principle that guides regulation of metabolic enzymes is that, in general, the body tries to keep cellular compounds in their highest energy form. That way the cells are most prepared for an activity that requires energy. Prime examples are that cells “prefer” high levels of ATP and low levels of ADP, and high levels of NADH2 and FADH2 and low levels of NAD and FAD. ATP, NADH2 and FADH2 are the higher energy forms of these compounds. The regulation of many enzymes depends on the concentrations of these metabolites. ADP, NAD, and FAD stimulate many enzymes, and ATP, NADH2 and FADH2 inhibit many enzymes. And often these are key, rate-limiting enzymes of metabolic pathways. Therefore, by regulating the activities of these enzymes, these substances effectively regulate entire pathways. When, for example, the concentration of ADP (the low energy form) increases in a muscle fiber, enzymes are stimulated, so reactions that are directly or indirectly involved in converting ADP to ATP speed up. When the concentration of ATP (the high energy form) increases in the muscle fiber, reactions involved in forming ATP are slowed down (when a high rate of ATP formation is not needed).

 
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Regulation of Metabolism (cont.)

Many individual chemical reactions are regulated in muscle and other tissues in the body. This regulation is complex, but the overall concept and the objective is simple. Cells must adjust to demands for energy placed on them (or they will die), and they try to provide the energy via aerobic metabolism first. Also, the body follows a carbohydrate-sparing principle. These statements are generalizations, however. There are exceptions to these general principles in certain tissues, and in certain situations, including many exercise situations.

 
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Use of the Terms Aerobic and Anaerobic

The terms “aerobic” and “anaerobic” are used with different definitions in different settings. I want to discuss some of the different uses of these and related terms here.

  • Aerobic – Literally, “requiring oxygen.”

  • Anaerobic – Literally, “requiring no oxygen.”

  • Aerobic metabolism – Metabolic reactions that require use of oxygen, directly or indirectly (e.g., reactions of the Krebs Cycle, beta oxidation and electron transport system).

  • Anaerobic metabolism – Metabolic reactions that do not use oxygen, directly or indirectly (e.g., anaerobic glycolysis).

  • Aerobic exercise – In exercise physiology, “aerobic exercise” is “exercise in which more than half of the energy for ATP formation comes from aerobic metabolism during the exercise.” This would include all exercise except maximal-effort exercise of about 2 minutes or less. In nonprofessional and some clinical settings, “aerobic exercise” typically refers to “any exercise bout that can be used to improve fitness of the oxygen transport and utilization systems, and especially endurance fitness.” (More about this below.)

  • Anaerobic exercise - In exercise physiology, “anaerobic exercise” is “exercise in which more than half of the energy for ATP formation comes from anaerobic metabolism during the exercise.” This would include only exercise of less than about 2 minutes in duration that involves maximal or near-maximal effort. In nonprofessional settings, "anaerobic exercise" typically refers to "all exercise that is not aerobic." (More about this below.)

 

 
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Use of the Terms Aerobic and Anaerobic (cont.)

"Aerobic and anaerobic terminology” was popularized by Dr. Kenneth Cooper, who founded the Aerobics Center in Dallas. In 1968, Dr. Cooper published his first book, “Aerobics.” He used the term to refer to a point system he developed for quantifying exercise based on its contribution to fitness of the oxygen transport system (which came to be known as “aerobic fitness”). By Dr. Cooper’s system, for example, jogging earned more “aerobic points” than playing golf, and walking earned more than weight-lifting. His system also set weekly point totals to be used as goals related to “aerobic training” (i.e., training that improved fitness of oxygen transport and utilization systems).

Over the years, “aerobics” took on the meaning of rhythmic activities (“aerobic dance”) that were good for aerobic training, and this is probably the most common use of the term “aerobics” today. Also, “aerobic exercise” has come to refer commonly to exercise that is appropriate for pursuing a certain fitness goal, namely improved “aerobic fitness.” Then everything else is categorized as “anaerobic exercise.”

 

 
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Use of the Terms Aerobic and Anaerobic (cont.)

Sometimes these definitions lead to absurdities. For example, it is common for people to refer to guidelines of the American College of Sports Medicine, which suggest, for example, that duration of exercise should be 20-60 minutes. This is just a guideline, suggesting that exercise bouts within this range of durations should provide a suitable aerobic training stimulus. Unfortunately, some take this guideline as Gospel and suggest something like, “To be aerobic, an exercise bout must be at least 20 minutes long.” A natural conclusion from a statement like this is that exercise that is 19 minutes long (or 19 minutes and 59 seconds!) is “not aerobic.” (Is it anaerobic?) Of course this is not true, no matter which of the definitions of “aerobic exercise” listed above is used.

This is not just trivial discussion of terminology. Telling people that their exercise essentially does no good if it’s not at least 20 minutes in duration is (a) factually incorrect; (b) dangerous for some (some should not exercise for more than a few minutes at a time until fitness improves); and (c) very discouraging for many; for individuals who are very unfit and/or who have been sedentary for a long time, but who are seriously considering starting an exercise program, 20 minutes of exercise is a target that is nearly impossible to hit.

 

 
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Use of the Terms Aerobic and Anaerobic (cont.)

Another absurdity that is often heard is that some very short-duration, light exercise (e.g., walking slowly for 2 or 3 minutes) is not aerobic. What is usually meant is that such exercise is not of sufficient intensity or duration to provide much training of the oxygen transport system for most people. (This is what should be stated.) Such exercise, however, is almost 100% aerobic in the physiological sense, and it certainly is not anaerobic.

I suggest that the term “aerobic exercise” can be effectively used in nonprofessional settings to refer to “exercise that stresses oxygen transport and utilization.” The ACSM guidelines relate to such exercise, but these should be used as guidelines only. For some, exercise of just a few minutes at a low intensity is appropriate aerobic exercise, with a long-term goal of increasing intensity and/or duration. I see no way or need to use the term “anaerobic exercise” in any other way than as used in exercise physiology as defined above. It may, however, be useful in certain situations to refer to the “anaerobic component” (e.g., small, medium, large) of certain exercise, especially contrasted with the “aerobic component.” This must be based on the underlying metabolism.

 
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Review of Lesson

You have come to the end of the online content of Unit 2 - Lesson 4. This is also the end of the content of the unit, not counting the two labs. If you have not already completed both of the labs associated with this unit (Lab 2 and Lab 3), you must do that to complete this unit on metabolism.

When you want to review the concepts in this lesson, use the Learning Objectives on Page 1 of this lesson and the Review Questions below. These should be a good study guide. If you can correctly do what the Objectives and Review Questions ask, you will have mastered the most important concepts in this lesson. Please realize, however, that these do not exhaustively cover all the information in the lesson.

When you review the entire unit, you should use the Learning Objectives listed for all four of the lessons and both labs (Labs 2 and 3).

If you are uncertain about any Objective or Review Question, or if you want clarification or expansion of any point in the lesson or unit, I urge you to start a threaded conference discussion on WebBoard. Other students may have the same concerns, will probably benefit from the discussion, and may have the information you seek. And, of course, feel free to contact me (Dr. Eldridge) for assistance.

Be sure to check the Announcements Page to see whether there is a specific WebBoard or other assignment associated with this lesson.

Review Questions

1.  List five specific examples of training activities that you have experience with or have observed. Analyze each in terms of metabolism: What system is predominantly stressed? What adaptation is likely to occur in response to the training?

2.  Select a specific exercise activity, such as from athletic competition, that may be limited by metabolism. Briefly describe a training program that would improve performance because of a metabolic adaptation. Explain the physiological basis of the improvement.

3.  State at least two specifics ways you have heard the terms "aerobic" and "anaerobic" used. Clarify the meaning of the terms in each case, and compare the meaning with the strict definitions used in physiology.