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Most individuals eat at least three meals a day. Eating is necessary to provide the
energy that is essential for all cellular and thus bodily activity. To provide this
energy, food must be transformed into chemical energy.

The total of all energy transformations that occur in the body is called metabolism.
When energy is used to build tissues as when amino acids are combined to form
proteins that make up muscles the process is called anabolism. When energy is
produced from the breakdown of food stuffs and stored so that it is available to
do work, the process is called catabolism.
The chemical energy produced from the food fuel is stored as adenosine
triphosphate (ATP). The ATP then transfers its energy to energy-
requiring physiological functions, such as muscle contraction during
exercise, in which some energy performs the work and some is
converted into heat. Thus, ATP is stored chemical energy that links the
energy-yielding and the energy-requiring functions within all cells. The
aim of this chapter is to fully explain ATP and how it is produced from
carbohydrate, fat, and protein food sources.
 ADENOSINE TRIPHOSPHATE (ATP)
Structurally, ATP is composed of a carbon-nitrogen base called adenine, a 5-carbon sugar
called ribose, and three phosphates, symbolized by Pi (inorganic phosphate). Each
phosphate group is linked by a chemical bond. When one phosphate is removed, the
remaining compound is adenosine diphosphate (ADP). When two phosphates are
removed, the remaining compound is adenosine monophosphate (AMP).

The ATP energy reaction is reversible. When ATP is synthesized from ADP and Pi, energy

is required. The addition of Pi is known as phosphorylation.

ADP + Pi + energy → ATP

When ATP is broken down, energy is released.

Hydrolysis is a chemical process in which a substance is split into simpler
compounds by the addition of water. ATP is split by hydrolysis.

ATP → ADP + Pi + energy for work + heat

The energy-requiring and energy-releasing reactions involving ATP are coupled

reactions. Coupled reactions are linked chemical processes in which a change in
one substance is accompanied by a change in another; that is, one of these
reactions does not occur without the other.
ATP can be resynthesized from ADP in three ways:
1. By interaction of ADP with CP (creatine phosphate, which is sometimes designated as
PC, or phosphocreatine).

2. By anaerobic respiration in the cell cytoplasm.

3. By aerobic respiration in the cell mitochondria.

Phosphocreatine is another high-energy compound stored in muscles. It transfers its

phosphate—and, thus, its potential energy—to ADP to form ATP, leaving creatine:

ADP + PC → C + ATP
 CELLULAR RESPIRATION
The process by which cells transfer energy from food to ATP in a stepwise series of
reactions is called cellular respiration. This term is used because, to produce energy,
the cells rely heavily on the oxygen that the respiratory system provides. In addition,
the by-product of energy production, carbon dioxide, is exhaled through the
respiratory system. Cellular respiration can be either anaerobic or aerobic. Anaerobic
respiration means it occurs in the absence of oxygen, does not require oxygen, or does
not use oxygen. Aerobic means it occurs in the presence of oxygen, requires, or
utilizes oxygen. Brain cells cannot produce energy anaerobically, and cardiac muscle
cells have only a minimal capacity for anaerobic energy production. Skeletal muscle
cells, however, can produce energy aerobically and/or anaerobically as the situation
demands.
 STEPS OF CELLULAR RESPIRATION
1. All three major food nutrients, fats (FAT), carbohydrates (CHO), and proteins
(PRO), can serve as fuel or substrates—the substances acted upon by enzymes—
for the production of ATP.
2. The most important immediate forms of the substrates utilized are glucose (GLU),
free fatty acids (FFA), and amino acids (AA). Both FFA and glycerol are derived
from the breakdown of triglycerides. Some cells can use glycerol directly in
glycolysis, but muscle cells cannot.
3. Acetyl coenzyme A (acetyl CoA) is the central converting substance (usually called
the universal or common intermediate) in the metabolism of FAT, CHO, and
PRO. Although the process of glycolysis provides a small amount of ATP as well
as acetyl CoA, both beta-oxidation and oxidative deamination or transamination
are simply preparatory steps by which FFA and AA are converted to acetyl CoA.
4. Each of the energy-producing processes or stages (glycolysis, Krebs cycle) consists
of a series of steps. Each step represents a small chemical change to a substrate
resulting in a slightly different product in a precise, unvarying sequence with
designed first and last steps. This is known as a metabolic pathway. That is, a
metabolic pathway is a sequence of enzyme-mediated chemical reactions
resulting in a specific product. Each stage may be made up of one or more
metabolic pathways. These sequences of steps are important for the body
because they allow energy to be released gradually. If all of the energy contained
in food nutrients were released at one time, it would be predominantly released
as heat and would destroy tissues.
 ANAEROBIC METABOLISM DURING EXERCISE
Once produced, ATP is stored in the muscle. This amount is relatively small and can
provide energy for only 2–3 seconds of maximal effort (Mougios, 2006).

However, another high-energy compound, phosphocreatine (PC), also known as

creatine phosphate (CP), can be used to resynthesize ATP from ADP almost
instantaneously. The amount of PC stored in muscle is about three times that of
ATP (Gollnick and King, 1969).

Muscles differ in the amount of stored PC by fiber type. Fast-twitch fibers have
proportionally more PC than ATP compared to slow-twitch oxidative fibers.
Any time the energy demand is increased—whether the activity is simply turning a
page of this book, coming out of the blocks for a sprint, or starting out on a long
bicycle ride—at least part of the immediate need for energy is supplied by these
stored forms (ATP, PC), which must ultimately be replenished. These sources are
also used preferentially in high-intensity, very short-duration activity. Most
resynthesis of ATP from PC takes place in the first 10 seconds of maximal muscle
contraction; little, if any, occurs after 20 seconds of maximal activity (Gastin,
2001) This ATP-PC system neither uses oxygen nor produces lactic acid (LA)
and is thus said to be alactic anaerobic.
 ANAEROBIC ENERGY PRODUCTION
A lactic Anaerobic PC Production:-

As previously described, alactic anaerobic production of ATP involves the

use of phosphocreatine (PC), which is simply creatine bound to
inorganic phosphate.

Close to 95% of the creatine in the body is stored in skeletal muscle. Thirty
to forty percent is stored as free creatine and the rest as
phosphocreatine. The process continues until the resting levels of both
PC and ATP are regained.
Specifically, when ATP is hydrolyzed by the contractile proteins in muscle (1) (large
inner circle), the resulting ADP is rephosphorylated in the cytoplasm by the PC
available there (2) (small inner circle). In turn, the free creatine is
rephosphorylated at the inner mitochondrial membrane from the breakdown of
ATP. The remnant (4) ADP is then free, in turn, to be phosphorylated again by
oxidative phosphorylation using energy substrates. In addition to providing ATP
rapidly, this mechanism, called the CP shuttle, is one way in which electron
transport and oxidative phosphorylation are regulated.
 LACTIC ACID/LACTATE PRODUCTION
Lactic acid is produced in muscle cells when the NADH + H+ formed in glycolysis is oxidized to
NAD+ by a transfer of the hydrogen ions to pyruvic acid (C3H4O3), which in turn is reduced to
lactic acid (C3H6O3).

In muscle tissue, lactic acid is produced in amounts that are in equilibrium with pyruvic acid under
normal resting conditions. In addition, lactic acid is always produced by red blood cells, portions
of the kidneys, and certain tissues within the eye. Both resting and exercise values depend on the
balance between lactic acid production (appearance) and removal (disappearance or clearance).
This balance of appearance and disappearance is called turnover. When production exceeds
removal, lactate is said to accumulate. The issues, then, especially during exercise, focus on what
conditions result in lactic acid production and what processes lead to lactic acid removal.
FACTORS AFFECTING LACTATE ACID PRODUCTION

1. Muscle contraction. During exercise, muscle activity obviously increases. Muscle contraction involves the

release of calcium (Ca2+) from the sarcoplasmic reticulum. In addition to its role in the coupling process of

actin and myosin, calcium also causes glycogenolysis by activating the enzyme glycogen phosphorylase.

Glycogen is processed by fast glycolysis and results in the production of lactic acid regardless of whether

oxygen levels are sufficient or not.

2. Enzyme activity. The conversion of pyruvate and NADH + H+ to lactate and NAD+ is catalyzed by specific

isozymes of the enzyme lactic dehydrogenase (LDH), whereas the conversion of pyruvate to acetyl CoA

(Stage II) prior to entry into the Krebs cycle is catalyzed by the enzyme pyruvate dehydrogenase (PDH).

LDH has the highest rate of functioning of any of the glycolytic enzymes and is much more active than the

enzymes that provide alternate pathways for pyruvate metabolism, including PDH and the rate limiting

enzymes in the Krebs cycle. Any increase in pyruvate and NADH + H+ further increases the activity of

LDH and results in the production of lactic acid (Spriet et al., 2000). Therefore, lactic acid production is an

inevitable consequence of glycolysis

3. Muscle fiber type. During high-intensity, short duration activities, fast-twitch glycolytic
(FG) muscle fibers are preferentially recruited. These fast-contracting glycolytic fibers
produce lactic acid when they contract, regardless of whether oxygen is present in
sufficient amounts or not. This response appears to be a function of the specific lactic
dehydrogenase isozyme and the low mitochondrial density found in these fibers.

4. Sympathetic neurohormonal activation. During heavy exercise, activity of the

sympathetic nervous system stimulates the release of epinephrine and glucagon and
suppression of insulin (see Figure 2.17). The result is the breakdown of glycogen,
leading ultimately to high levels of glucose-6-phosphate (G6P). High levels of G6P
increase the rate of glycolysis and thus the production of pyruvic acid (Brooks, 1986).
As previously described, any increase in pyruvate and NADH + H+ ultimately results
in an increase in lactic acid.
5. Insufficient oxygen (anaerobiosis, onset of anaerobic metabolism). Finally, during
high-intensity, short duration or near-maximal exercise or during static
contractions when blood flow is impeded (Stallknecht et al., 1998), the delivery
of oxygen to the mitochondria— and thus the availability of oxygen as the final
oxygen acceptor at the end of the respiratory chain— can become deficient. In
these circumstances, glycolysis proceeds at a rate that produces larger quantities
of NADH + H+ than the mitochondria have oxygen to accept.
Thus, although lactic acid is associated with high intensity, short-duration exercise,
this is not the only exercise condition that results in the production of lactic acid.
Furthermore, although a lack of oxygen can contribute to the production of
lactic acid, the presence of lactic acid does not absolutely indicate a lack of
oxygen. The presence of lactic acid simply reflects the use of the anaerobic
glycolytic pathway for ATP production and the balance between glycolytic and
mitochondrial activities. Furthermore, rather than lactic acid being a “waste
product,” lactate provides a means of coordinating carbohydrate metabolism in
diverse tissues (Brooks, et al., 2000). The formation, distribution, and utilization
of lactate is a way for glycogen reserves to be mobilized and used within either
the working muscle cell or other cells. In the process, blood glucose is spared for
use by other tissues.
LACTATE CLEARANCE
Blood lactate levels reflect the balance between lactic acid production (appearance) and clearance
(removal). Lactate clearance occurs primarily by three processes: oxidation (50–75%),
gluconeogenesis/glyconeogenesis (10–25%), and transamination (5–10%). All three processes
can involve the movement of lactate, either within or between cells. As stated previously,
although produced as lactic acid, at physiological pH more than 99% quickly dissociates into
lactate (La−) anions and protons (H+) (Gladden, 2004). Lactate moves readily between
cytoplasm and mitochondria, muscle and blood, blood and muscle, active and inactive
muscles, glycolytic and oxidative muscles, blood and heart, blood and liver, and blood and
skin (Brooks, 2000). Transport across cellular and mitochondrial membranes occurs by
facilitated exchange down concentration and hydrogen ion (pH) gradients using lactate
transport proteins known as monocarboxylate transporters (MCTs)
A small amount of lactate in the circulation moves from the blood to the skin and
exits the body in sweat. Finally, some lactate remains as lactate circulating in the
blood. This comprises the resting lactate level. Oxidation is by far the
predominant process of lactate clearance both during and after exercise. As
stated previously, the accumulation of lactate in the blood depends on the
relative rate of appearance (production) and disappearance (clearance), which in
turn is directly related to the intensity and duration of the exercise being done.
 THE ANAEROBIC EXERCISE RESPONSE
Oxygen Deficit and Excess Post-exercise Oxygen Consumption: (EPOC)-
When exercise begins, regardless of how light or heavy it is, there is an immediate
need for additional energy. Thus, the most obvious exercise response is an
increase in metabolism. All three energy systems are involved in this response,
their relative contributions being proportional to the intensity and duration of
the activity. In Figure 2.3A, the activity is a moderate submaximal bout. The
oxygen requirement for this exercise is 1.4 L·min−1. The individual has a
V.O2max of 2.5 L·min−1. Therefore, this individual is working at 56% V.O2max.
. This difference between the oxygen required during exercise and the oxygen
supplied and utilized is called the oxygen deficit. Because of this discrepancy
between supply and demand, anaerobic sources must be involved in providing
energy at the onset of all activity. The O2 deficit has traditionally been explained
as the inability of the circulatory and respiratory systems to deliver oxygen
quickly enough to meet the increased energy demands.
during the transition from rest to work, energy is supplied by:
1. O2 transport and utilization.
2. Utilization of O2 stores in capillary blood and bound to myoglobin.
3. The splitting of stored ATP-PC.
4. Anaerobic glycolysis, with the concomitant production of LA

if the exercise intensity is low enough (as in the example in Figure 2.3A), the aerobic
system will predominate and the oxygen supply will equal the oxygen demand.
This condition is called steady-state, steady rate, or steady-level exercise.
Figure 2.3B shows a smoothed plot of O2 consumption at rest and during and after
an exercise bout in which the energy requirement is greater than V.O2max,
sometimes called supramaximal exercise.
DURING RECOVERY METABOLISM RETURN TO
RESTING LEVEL ?
During recovery from exercise represented by the concave curves obtained after
exercise in both Figures 2.3A and 2.3B, oxygen consumption drops quickly (a
fast component lasting 2–3 min) and then tapers off (a slow component lasting
3–60 min). The magnitude and duration of this elevated post exercise oxygen
consumption depends on the duration, intensity, and modality of the preceding
exercise. After light submaximal work (Figure 2.3A), recovery takes place
quickly; after heavy exercise (Figure 2.3B) recovery takes much longer.
period of elevated metabolism after exercise has been called the O2 debt. EPOC is
defined as the oxygen consumption during recovery that is above normal resting
values. The relationship between the size of the EPOC and the intensity of
aerobic exercise is curvilinear, whereas the relationship between the size of the
EPOC and the duration of aerobic exercise in more linear
IMPORTANCE OF RECOVERY:
1-Restoration of ATP-PC stores: About 10% of the EPOC is utilized to
rephosphorylate creatine and ADP to PC and ATP, respectively, thus restoring
these substances to resting levels.
2-. Restoration of O2 stores: Although the amount of O2 stored in the blood (bound
to hemoglobin) and muscle (bound to myoglobin) is not large, it does need to be
replenished when exercise stops. Replenishment probably occurs completely
within 2–3 minutes.
3-3. Elevated cardiovascular-respiratory function: Both the respiratory system and
the cardiovascular system remain elevated post exercise; that is, neither the
breathing rate and depth nor heart rate recovers instantaneously. Although this
enables the extra amounts of oxygen to be processed, the actual energy cost of
these cardiovascular-respiratory processes probably accounts for only 1–2% of
the excess oxygen
4. Elevated hormonal levels: During exercise the circulating levels of the catecholamines
(epinephrine and norepinephrine), thyroxine, and cortisol are all increased. In
addition to their fuel mobilization and utilization effects, these hormones increase
Na+–K+ pump activity in muscles and nerves by changing cell membrane
permeability to Na+ and K+. As an active transport process, the Na+-K+ pump
requires ATP. The increased need for ATP means an increased need for O2. Until the
hormones are cleared from the bloodstream, the additional O2 and ATP use is a
significant contributor to the EPOC. (excess post-exercise oxygen consmption)
5. Lactate removal: The lactate that has accumulated must be removed. Historically, it
was thought that the majority of this lactate was converted to glycogen and that this
conversion was the primary cause of the slow component of EPOC.
6.Elevated body temperature: When ATP is broken down to supply the energy for
chemical, electrical, or mechanical work, heat is produced as a by-product. During
exercise, heat production may exceed heat dissipation, causing a rise in body core
temperature. Thus, in recovery, although high levels of energy are no longer needed to
support the exercise, the influence of the elevated temperature remains, because
cooling takes some time to occur.
 LACTATE CHANGES
Lactate levels in response to exercise depend primarily on the intensity of the
exercise. Acute exercise does not result in any meaningful enhancement of lactate
transporters. Instead, transmembrane lactate and hydrogen ion gradients
increase. Lactate transport is faster in oxidative fibers than in glycolytic ones.
The fast transport of lactate by oxidative fibers may reflect lactate’s role as an
energy substrate, while the slower transport in glycolytic fibers may contribute
to a greater retention of lactate during recovery for reconversion into glycogen
(Gladden, 2000).
SHORT-TERM, HIGH-INTENSITY ANAEROBIC EXERCISE

Figure 2.4 includes muscle and blood lactate response to high-intensity, short-
duration (3 min or less), supramaximal exercise. As the figure shows, muscle
lactate levels rise immediately with the onset of such hard work (105–110%
V.O2max) and continue to raise throughout the length of the task. Blood lactate
values show a similar pattern, if the lag for diffusion time is taken into account.
This lactate response (a rapid and consistent accumulation) is representative of
what occurs when the exercise bout is greater than 90% V.O2max.
SHORT- AND LONG-TERM, LIGHT TO MODERATE
SUBMAXIMAL AEROBIC EXERCISES
Figure 2.5 depicts what occurs in both short-term and long-term low-intensity
submaximal aerobic activities. During the first 3 minutes of such steady-state
work the lactate (La−) level rises (Figure 2.5A). This increase reflects the lactate
accumulated during the oxygen deficit. When a similar workload is continued
for 60 minutes, the lactate level remains unchanged after the initial rise (Figure
2.5B). The reason for this result lies in the balance between lactate production
(the rate of lactate appearance) and lactate clearance (the rate of lactate
disappearance).
LONG-TERM, MODERATE TO HEAVY SUBMAXIMAL
AEROBIC EXERCISE:-
in Figure 2.8. Two groups of runners were matched according to their V.O2max. One
group ran a simulated marathon on the treadmill at 73.3% V.O2max (in 2 hr 45
min or less); the other group ran the same distance but at 64.5% V.O2maxin 3 hr
45 min or slightly less). Within the slow group, blood lactate values remained
relatively stable and at a level considered to be within normal resting amounts.
The blood lactate levels in the fast group were statistically significantly higher
throughout the marathon than those of the slow group. As absolutes, however,
both sets of values were low, with the slow group being within a normal resting
range and the fast group slightly above normal resting levels (O’Brien et al., 1993).
In general, during light to moderate work (that is, less than 50–60% of V.O2max),
the blood lactate level is likely to rise slightly at first. Then it either remains the
same or decreases slightly, even if the exercise lasts 30–60 minutes. At moderate
to heavy intensities between 50 and 85% V.O2max (depending on the
individual’s genetic characteristics and training status), lactate levels rise rapidly
during the first 5–10 minutes of exercise. If the workload continues for more
than 10 minutes, the lactate level may continue to rise, may stabilize, or may
decline, depending on the individual and other conditions.
INCREMENTAL AEROBIC EXERCISE TO MAXIMUM:-

Figure 2.9 depicts the accumulation of lactate during incremental exercise to

maximum. Oxygen consumption (Figure 2.9A) increases in a rectilinear pattern
to meet the increasing demands for energy, but blood lactate Figure 2.9B) shows
very little initial change and then increases continuously (Hughes et al., 1982;
Hughson et al., 1987).
The original concept of an anaerobic threshold is based on the lactate response to
incremental exercise, as depicted in Figure 2.10, and the relationship of the lactate
response to minute ventilation (the volume of air breathed each minute). As
espoused by Wasserman et al. (1973), the anaerobic threshold is defined as the
exercise intensity, usually described as a percentage of V.O2max or absolute
workload, above which blood lactate levels rise and minute ventilation increases
disproportionately in relation to oxygen consumption. The onset of anaerobic
metabolism (or anaerobiosis), which is assumed to lead to the lactate accumulation,
is attributed to the failure of the cardiovascular system to supply the oxygen
required to the muscle tissue. The disproportionate rise in ventilation is attributed
to excess carbon dioxide resulting from the buffering of the lactic acid.
 ASSIGNMENT 1
WHAT IS THE RELATION BETWEEN THE LACTIC
ACID AND THE VENTILATION DURING
INCREMENTAL EXERCISE?
Lactic acid is a strong acid, it readily dissociates into hydrogen ions (H+) and lactate
(La−). Because excess hydrogen ions would change the pH (or acid-base balance)
of the muscles and blood, the body attempts to bind these hydrogen ions to a
chemical buffer. For example, sodium bicarbonate (a weak base) may be used as
a buffer in the reaction:
NaHCO3 + HLa « NaLa + H2CO3 sodium bicarbonate + lactic acid « sodium lactate
+ carbonic acid. Carbonic acid is a much weaker acid than LA and can be
further dissociated into water and carbon dioxide:
H2CO3 « H2O + CO2
Carbon dioxide is a potent stimulant for respiration and can easily be removed from
the body through respiration, thereby assisting in the maintenance of pH (Pitts,
1974). The carbon dioxide thus formed is said to be nonmetabolic carbon dioxide,
since it does not result from the immediate breakdown of an energy substrate
(carbohydrate, fat, or protein).
 ASSIGNMENT 2
WHY IS LACTIC ACID ACCUMULATION A
PROBLEM?
It is the hydrogen ions (H+) that dissociate from lactic acid, rather than undissociated lactic
acid or lactate (La−), that present the primary problems to the body. This distinction is
important because at normal pH levels, 99% of the lactic acid is dissociated immediately
to H+ and La- (C3H5O- 3) (Brooks, 1985; Gladden, 2004). As long as the amount of free
H+ does not exceed the ability of the chemical and physiological mechanisms to buffer
them and maintain the pH at a relatively stable level, there are few problems. Most
problems arise when the amount of lactic acid—and thus H+— exceeds the body’s
immediate buffering capacity and the pH decreases (Gladden, 2004). The blood has
become more acidic. At that point pain is perceived and performance suffers. The
mechanisms of these results are as follows.
Pain
Anyone who has raced or run the 400-m distance all out understands the pain associated
with lactic acid accumulation. The 400-m run takes between approximately 45 seconds
and 3 minutes (depending on the ability of the runner) and relies heavily on the ATP-PC
and LA systems to supply the needed energy. The resultant hydrogen ions accumulate
and stimulate pain in the nerve endings in the muscle (Guyton and Hall, 2006).
Metabolic Fatigue
Metabolic fatigue results from a reduced production of ATP linked to enzyme
changes, changes in membrane transport mechanisms, and changes in substrate
availability. Enzymes—in particular, the rate-limiting enzymes in the metabolic
pathways—can be inactivated by high hydrogen ion concentrations (low pH). The
hydrogen ion attaches to these enzyme molecules and in so doing changes their size
and shape and thus their ability to function. Phosphofructokinase (PFK) is thought
to be particularly sensitive, although oxidative enzymes can also be affected.
Muscular fatigue
is evidenced by reduced force and velocity of muscle contraction. Suffice it to say here
that the lactic acid hypothesis of muscular fatigue is based primarily on two major
effects of a lowered pH on muscle contraction. The first is an inhibition of
actomyosin ATPase, the enzyme responsible for the breakdown of ATP to provide the
immediate energy for muscle contraction. The second is an interference of H+ with
the actions and uptake of calcium (Ca2+) that is necessary for the excitation-
contraction coupling and relaxation of the protein cross-bridges within the muscle
fiber. High levels of lactate ions (La−) may also interfere with cross-bridging
(Gladden, 2004; Hogan et al., 1995).
THANK YOU