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Unit 2 - Energy Metabolism : Lesson 1

KINE xxxx Exercise Physiology

Course: KINE xxxx Exercise Physiology

3 Unit 2 - Energy Metabolism 2 Lesson 1 1 U2L1P1

- Introduction to Unit 2 - 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.

Contents of Lesson 1:

Description Page Introduction to Unit 2 - Lesson 1 1-2Definitions of Energy Metabolism, Catabolism and Anabolism 3-5

ATP – General Considerations 6-8Formation of ATP 9Formation of ATP - The CK Reaction 10-12Formation of ATP – Anaerobic Glycolysis 13-15Formation of ATP – Aerobic Metabolism 16-27



Formation of ATP – Aerobic Metabolism 16-27Formation of ATP – Summary 28Review of Lesson 29

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- Introduction to Unit 2 - Lesson 1 (cont.)

Outline of Content

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. Descriptionb. Advantages and disadvantages (limitations)

2. Anaerobic glycolysis

a. Descriptionb. Advantages and disadvantages (limitations)

3. Aerobic (oxidative) metabolism

a. General descriptionb. 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



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



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.

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.

The limitation of anaerobic glycolysis is that the end product, 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



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.

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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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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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



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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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



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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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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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



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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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.

End products 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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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 end products of these reactions. The end products 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 end products 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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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.

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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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



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 end product? 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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Key:

U2L1P29

- 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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