Download Content Display : Unit 2 - Energy Metabolism : Lesson 1

Content Display : Unit 2 - Energy Metabolism : Lesson 1
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Content Display
Unit 2 - Energy Metabolism : Lesson 1
Course: KINE xxxx Exercise Physiology
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
1-2
Definitions of Energy Metabolism, Catabolism and
3-5
Anabolism
ATP – General Considerations
6-8
Formation of ATP
9
Formation of ATP - The CK Reaction
10-12
Formation of ATP – Anaerobic Glycolysis
13-15
Formation of ATP – Aerobic Metabolism
16-27
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Formation of ATP – Aerobic Metabolism
16-27
Formation of ATP – Summary
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Review of Lesson
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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. 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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U2L1P3
- 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
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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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U2L1P6
- 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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U2L1P7
- 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.
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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
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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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U2L1P12
- 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
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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
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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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U2L1P16
- 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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U2L1P17
- 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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- 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).
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The Krebs Cycle starts with a reaction that combines the 2carbon 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
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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
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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.
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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
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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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U2L1P23
- 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.
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.
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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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U2L1P24
- Formation of ATP – Aerobic Metabolism (cont.)
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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U2L1P25
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U2L1P25
- 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 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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U2L1P26
- 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.)
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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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U2L1P27
- 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
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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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U2L1P28
- 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
Max
power
1.00
(kcal/sec)
Minimum
0
response
(Immediate)
time (sec)
29
50
2,000
100,000
0.50
0.25
0.12
15
120
---
U2L1P29
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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.
Cancel
Key:
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