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Bioenergetic provision of energy for muscular activity
Bioenergetic provision of energy for muscular activity
Greg D. Wells, Ph.D.1*, Hiran Selvadurai, M.D.2, Ingrid Tein, M.D.3
1
Department of Physiology and Experimental Medicine, The Hospital for Sick Children,
Toronto, Canada & Department of Anesthesiology, The Toronto General Hospital, 2Paediatrics
& Child Health, Children's Hospital, Westmead, 3Division of Neurology, Department of
Pediatrics, The Hospital for Sick Children, University of Toronto, Canada
Running head: Bioenergetic provision of energy for muscular activity
*Corresponding author:
Greg D. Wells, Ph.D.
Division of Respiratory Medicine, Rm. 4534,
The Hospital for Sick Children,
555 University Avenue,
Toronto, Ontario, Canada M5G 1X8
Tel.: 1-416-710-4618
Fax: 1-416-813-5109
E-mail: [email protected]
Ingrid Tein, M.D.
Email: [email protected]
Hiran Selvadurai, M.D.
Email: [email protected]
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Bioenergetic provision of energy for muscular activity
Abstract
A complex series of metabolic pathways are present in human muscle that break down substrates
from nutritional sources to produce energy for different types of muscular activity. However,
depending on the activity in which an individual is engaged, the body will make use of different
energy systems that have been adapted for the particular activity. More specifically, utilization of
bioenergetic substrates depends on the type, intensity, and duration of the exercise. The aerobic
oxidative system is used for longer duration activities of low to moderate intensity, the anaerobic
glycolytic system is used for short to moderate duration activities of higher intensity, and the
high energy phosphagen system is used for short duration activities of high intensity. The
efficiency and effectiveness of these pathways can be enhanced through physical activity and
training. It is these bioenergetic pathways that are the focus of this review.
Key Words:
Exercise, physiology, aerobic, anaerobic, respiratory, metabolism
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Bioenergetic provision of energy for muscular activity
Introduction
Humans are capable of performing amazing feats. Sprinters run down the track with astonishing
speed and power; power lifters make hundreds of kilograms look like a sack of potatoes;
swimmers traverse an entire lake or channel against the elements; hurdlers gracefully clear all
obstacles in their way; and some basketball players even seem to defy the laws of gravity. Before
muscles can produce movement by pulling on their attachments to bones, they must first obtain a
source of energy to sustain such a movement. A complex series of metabolic pathways are
present in human muscle that break down substrates from nutritional sources to produce energy
for different types of muscular activity. However, depending on the activity in which an
individual is engaged, the body will make use of different energy systems that have been adapted
for the particular activity (see Figure 1) (1). More specifically, utilization of bioenergetic
substrates depends on the type, intensity, and duration of the exercise (2). The aerobic oxidative
system is used for longer duration activities of low to moderate intensity, the anaerobic
glycolytic system is used for short to moderate duration activities of higher intensity, and the
high energy phosphagen system is used for short duration activities of high intensity. The
efficiency and effectiveness of these pathways can be enhanced through physical activity and
training. It is these bioenergetic pathways that are the focus of this review.
<<Insert Figure 1 near here>>
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Bioenergetic provision of energy for muscular activity
An overview of muscle physiology
Muscle tissue - the contraction specialist - provides a prime example of how the structure of a
tissue is well-adapted to perform a specific function. With approximately 324 muscles, and with
muscle constituting 30-35% and 42-47% of body mass in women and men, respectively the
importance of muscular activity is obvious. The various types of muscle tissue support numerous
life functions such as ventilation, physical activity and exercise, digestion, and of course,
pumping life-sustaining blood throughout the body via specialized cardiac muscle. Skeletal
muscle (also termed striated muscle) connects the various parts of the skeleton through one or
more connective tissue tendons and is the type of muscle used to produce movement during
exercise. During muscle contraction, skeletal muscle shortens and, as a result of the tendinous
attachments, functions to move the various parts of the skeleton with respect to one another via
joints. This allows changes in position of one skeletal segment in relation to another, thus
creating movement. Skeletal muscle is comprised of numerous multinucleated cylinder-shaped
cells called muscle fibres (myofibrils), and each fibre is made up of a number of myofilaments.
Physically, they range in size from under a hundred microns in diameter and a few millimeters in
length to a few hundred microns across and a few centimetres in length. Each cell (fibre) is
surrounded by a connective tissue sheath called the sarcolemma, and a variable number of fibres
are enclosed together by a thicker connective tissue sheath (the perimysium) to form a bundle of
fibres called fascicles. Each fibre contains not only the contractile machinery needed to develop
force (sarcomeres), but also the cell organelles necessary for cellular respiration (mitochondria).
Each fibre is activated through electrical impulses transmitted by nerves, the motor nerves and
motoneurons in particular. A group of fibres activated via the same nerve is termed a motor unit.
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Also located outside each fibre is a supply of capillaries from which the cell obtains nutrients and
eliminates waste.
Within each myofibril, a number of contractile units called sarcomeres, are organized in series,
i.e., attached end to end. Each sarcomere is comprised of three types of protein myofilaments:
the thick filament system is composed of myosin protein which is connected from the M-line to
the Z-disc by the protein titin. It also contains myosin-binding protein C which binds at one end
to the thick filament and the other end to the protein actin. The thin filaments are assembled by
actin monomers bound to nebulin, in a process that also involves tropomyosin. Nebulin and titin
give stability and structure to the sarcomere (see Figure 2). When a signal comes from the motor
nerve activating the fibre, the neurotransmitter acetylcholine is released and travels across the
neuromuscular junction. The action potential then travels along T (transverse) tubules until it
reaches the sarcoplasmic reticulum. The action potential from the motor neuron changes the
permeability of the sarcoplasmic reticulum, allowing the flow of calcium ions into the
sarcomere. Outflow of calcium from the sarcoplasmic reticulum allows the heads of the myosin
filaments to temporarily attach themselves to the actin filaments, a process termed “cross bridge
formation”. The movement of the cross bridges causes a movement of the myosin filaments in
relation to the actin filaments, leading to shortening of the sarcomere, and muscle contraction.
Human skeletal muscle is composed of a mixture of two contractile fibre types: slow twitch and
fast twitch fibres. Each of the fibre types can be described on the basis of its predominant
metabolic pathway by which it derives energy, with the type I slow twitch fibres being described
as oxidative (Type I or SO), and the fast twitch fibres being subdivided into two sub-groups, fast
twitch oxidative-glycolytic (Type IIa or FOG) and fast twitch glycolytic (Type IIb or FG). Each
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of the three fibre types described above have distinctive morphological, contractile, and
metabolic characteristics (see Table 1).
<<Insert Table 1 near here>>
<<Insert Figure 2 near here>>
The chemistry of energy production in human muscle
All energy in the human body is derived from the breakdown of complex nutrients such as
carbohydrates, fats, and proteins (3). The end result of the breakdown of these substances is the
production of the adenosine triphosphate (ATP) molecule, the energy currency of the body. ATP
provides all the energy for fuelling biochemical processes of the body such as muscular work or
the digestion of food. The capacity to perform muscular work (work = force exerted x distance
moved) is dependent on supplying sufficient energy at the required rate for the duration of the
activity.
Energy is liberated for work when the chemical bond between ATP and its phosphate sub-group
is broken through hydrolysis when catalyzed by the enzyme ATPase:
Equation 1:
ATP breakdown:
ATP +  ADP + Pi + Energy
ATP is broken down in a process called “ATP turnover”. Water (H2O) hydrolyzes the unstable
chemical bonds of the phosphate groups of the ATP molecule, yielding an inorganic phosphate
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molecule (Pi) and adenosine diphosphate (ADP).”The released energy is about 38-42 kilojoules
(kJ) or 9-10 kilocalories (kcal) per mole of ATP (4).
The body harnesses this energy when the free Pi group is transferred to another molecule. When
this other molecule is joined with the new free phosphate group, it is said to be phosphorylated.
All muscular work done in the body depends upon these phosphorylated molecules. For
example, ATP powers the movement of muscles by transferring phosphates to contractile
proteins, which leads to the contraction of muscle fibres (4).
When the body performs work, it needs a continuous supply of ATP, but the initial stores of ATP
in the muscles are used up very quickly. Therefore, ATP must be regenerated. ATP is a
renewable resource that can be regenerated by the recombination of ADP and Pi. The metabolic
process that results in the recombination of ADP and Pi to form ATP is termed ATP resynthesis
(see Equation 2). ATP can also be resynthesized through the combination of phosphocreatine
(PCR) and ADP as shown in Equation 3. This reaction can occur at a very fast pace in the body.
The resynthesis of ATP is described in the reactions below:
Equation 2:
ATP resynthesis:
ADP + Pi + energy  ATP
Equation 3:
ATP resynthesis:
PCr + ADP + energy  ATP + Cr
The regeneration of ATP, however, requires energy. This energy is supplied by the breakdown of
complex food molecules such as carbohydrates and fats in metabolic energy systems of the
human body. These energy systems will now be presented in more detail.
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The energy systems
The turnover and resynthesis of ATP involves three energy systems, each of which employs a
different means of energy production. These energy systems are (1) the high-energy phosphagen
system, (2) the anaerobic glycolytic system, and (3) the aerobic oxidative system (Table 2 and
Figure 3). These sources of energy for muscular contraction and other types of work are
designated as aerobic or anaerobic, depending on whether they require the presence of oxygen to
provide energy. The high-energy phosphagen and the anaerobic glycolytic systems do not use
oxygen. The aerobic oxidative system depends on oxygen to produce energy. The three
bioenergetic systems that are used in human physiology to produce energy for muscular activity
are explained in detail in the following sections.
<<Insert Table 2 near here>>
<<Insert Figure 3 near here>>
The High-Energy Phosphate System
The high-energy phosphate system (also known as the phosphagen or anaerobic alactic system)
is characterized by the substrates that the system uses to produce energy. This system can
provide energy for muscles in the initial 1 to 15 seconds of high intensity activity (5). The highenergy phosphate substrates that are the primary energy source for the high-energy phosphate
system are adenosine triphosphate (ATP) and phosphocreatine (PCr). During the initial stages of
high intensity exercise, ATP is broken down via the enzyme ATPase, and phosphocreatine is
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broken down via the enzyme creatine kinase to supply inorganic phosphate for ATP resynthesis
(Equations 2 and 3, respectively) (6).
The high-energy phosphate system can produce very large amounts of energy in a short duration
of time (from 2.4 mmol/kg/s in sedentary people to 10-15 mmol/kg/s in athletes) (7, 14). The
high-energy phosphate system can supply energy until the intramuscular stores of ATP are
decreased and, thereafter, for as long as there is a local supply of phosphocreatine to resynthesize
ATP from ADP. The total muscle stores of ATP (3.5-7.5 mmol/kg) and creatine phosphate (1628 mmol/kg) are small and are depleted rapidly in high intensity work (7, 14). Therefore, the
initial concentrations of high-energy phosphates in the muscle are limiting factors in an
individual's ability to perform short-term high intensity work. Once the stores of phosphocreatine
are depleted, ATP resynthesis must occur through anaerobic glycolysis or aerobic oxidation, and
the power output drops accordingly.
The high-energy phosphate system is the primary energy system that is used in sporting events
such as weight lifting, high jump, long jump, 100-metre run, or 25-metre swim. These high
power output activities require a high rate of energy production as the work is done over a short
time interval (power = work / time). It is also used for high intensity activities of daily living
such as jumping, or short runs. If individuals are to continue the activity beyond a 15-second
period, they must produce energy from another system at a lower power output.
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Training may result in changes in levels of stored ATP and PCr in muscle. Strength training
(repeated muscular efforts against a resistance or opposing force) may result in increases of
approximately 20% in ATP, and PCr (8). Sprint training (short high intensity intervals separated
by long rest periods) does not appear to result in increased stores of ATP or PCr (9). Strength
and sprint training modalities also appear to affect the enzymes associated with the high energy
phosphate system, more specifically ATPase and creatine kinase (10-12).
The Anaerobic Glycolytic System
The body relies primarily on anaerobic metabolism for the energy required to perform intensive
exercise of greater than 12-15 seconds and less than 3 minutes duration (4). Anaerobic glycolysis
is the primary energy system that is used in sporting events such as the 800-metre run, 200-metre
swim, downhill ski racing, and 1500-metre speed skating and in other activities such as sprints
during soccer or hockey games. Metabolically, energy production via glycolysis is accomplished
in the cytoplasm of skeletal muscle by the catabolism of carbohydrate, in the form of blood
glucose or muscle glycogen (the storage form of glucose, consisting of many molecules of
glucose), to pyruvate (3) through 10 separate but linked steps of the anaerobic glycolytic
pathway (13) (see Figure 4). This biochemical process results in the release of energy in the form
of ATP, which is then used for muscle contraction. During glycolysis certain enzymes break
down the chemical bonds in glucose in the absence of oxygen (hence the term anaerobic). Each
molecule of glucose ultimately yields 2 lactic acid molecules and 2 molecules of ATP, the latter
is then used for muscle contraction.
<<Insert Figure 4 near here>>
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Although the peak rate of energy production is high (1.6 mol ATP . min-1) , the system is
inefficient, as only 2 mols of ATP are produced for every one mol of glucose that is broken
down (14). Most of the energy generated in glycolysis does not result in ATP resynthesis.
Instead it is dissipated as heat. Further, two molecules of ATP contribute to the initial
phosphorylation of the glucose molecule, glycolysis generates a net gain of two ATP molecules.
This represents an endergonic conservation of 14.6 kcal/mol. Glycolysis generates only about 5
% of the total ATP generated during the complete breakdown of the glucose molecule. However,
owing to the high concentration of glycolytic enzymes and the speed of these reactions,
significant energy for muscle action is generated rapidly during glycolysis (14). Further, when
the rate of muscle work is high, pyruvate can accumulate faster than the aerobic oxidative system
can process, and is then converted into lactic acid. The conversion of pyruvate to lactic acid
production is used to maintain the rate of anaerobic glycolysis and energy production (15). This
process has recently been reviewed (16) and was the subject of a comprehensive symposium
(17).
The exercise intensity at which lactic acid begins to accumulate within the blood has been
commonly referred to as the anaerobic threshold (18). In practical terms, the anaerobic threshold
can be thought of as the point during exercise when the person begins to feel discomfort and a
burning sensation in their muscles. It can be identified during clinical incremental exercise tests
as the point when carbon dioxide production (VCO2) exceeds oxygen consumption (VO2) with
the resulting respiratory exchange ratio (RER) greater than one. Some investigators believe that
accumulation of lactic acid, which breaks down into lactate and hydrogen ions, will eventually
contribute to muscle fatigue. However, this would not account for the muscle fatigue, cramps
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and contractures seen during high-intensity, short-burst exercise in people with
glycolytic/glycogenolytic disorders, in which glycolysis, and thus lactate production, is blocked.
Thus, there are likely many different variables in the microenvironment of the muscle that
contribute to muscle fatigue under different conditions. For example, hydrogen ions may
interfere with the actin-myosin coupling and thereby ultimately impede muscle contraction.
Further, the pH change associated with the accumulation of hydrogen ions may decrease the rate
of glycolysis through its effect on the rate-limiting enzyme phosphofructokinase (PFK). These
mechanisms are reviewed in detail elsewhere (19).
Lactic acid accumulation is a commonly measured variable in sports physiology and typical
values range from 2 mmol/L at rest, to 4 mmol/L in moderate sustainable exercise to 16 mmol/L
in maximal anaerobic exercise (i.e. 2 minute maximal effort sprinting). Efficient lactate removal
from the Type II glycolytic muscle fibres, where lactic acid is predominantly produced, to Type I
oxidative fibres, where lactate can be oxidized in mitochondria, can allow individuals to
continue to exercise at higher intensities for longer periods of time. This transfer of lactic acid in
and out of muscle fibres is accomplished via monocarboxylate lactate transporters on the surface
of the muscle cell (20). A graphical representation of the physiology of lactic acid transport is
presented in Figure 5.
<<Insert Figure 5 near here>>
Exercise training has significant effects on the anaerobic glycolytic system. High intensity
interval training (e.g. 60 second maximal efforts alternating with 2-3 minutes of rest) can
increase the rate of flux through the glycolytic pathway, thus increasing the ATP production rate,
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but also increasing the rate of lactic acid production (21). This increased flux through the
glycolytic pathway is accomplished through upregulation of anaerobic enzymes. Muscle and
blood buffering capacity can also be increased through anaerobic sprint or interval training (22).
Trained individuals have also been shown to remove lactate faster from exercising muscle,
suggesting an increase in the number and/or efficiency of the lactate transporters present in the
specific muscle tissue (Type I or Type II) (23). Aerobic endurance training can also increase the
rate of lactate elimination by increasing the rate of pyruvate processing in the Krebs cycle in
mitochondria. This increases the work rate that can be achieved exclusively through aerobic
metabolism, and thus decreases the production of lactic acid for a given work level (24). Aerobic
endurance training can result in other adaptations that can lead to an increased rate of lactate
removal from the muscle following training, including increased muscle blood flow and
increased ability to metabolize lactate in the heart, the liver and in non-working muscle. Blood
flow is increased in trained individuals through an increase in the number of blood vessels in the
muscle, altered neural and endocrine function, more red blood cells, greater total blood volume,
and increased cardiac output (25).
The Aerobic Oxidative System
The aerobic oxidative energy system is a very important energy system in the human body, as it
is the primary source of energy for a very broad range of activities. Daily activities such as
walking, jogging, swimming, household chores, and walking up stairs all use energy provided by
the aerobic oxidative system. Exercise that is performed at an intensity lower than that of the
anaerobic threshold relies exclusively on the aerobic system for energy production. Thus, blood
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lactate levels remain relatively low (2-6 mmol/L blood) during purely aerobic exercise. As the
duration of intensive activity increases, the relative contribution of the aerobic oxidative system
to total energy production increases (see Figure 1) (26). During intense exercise, well trained
individuals can elevate their rate of oxygen consumption up to 20 times above resting values
(27). Under conditions of heavy exercise, the skeletal muscle cells set the aerobic demand for
oxygen, as 90% of the oxygen in the body is consumed in the mitochondria in the muscle cell.
The aerobic energy system is the primary energy system that is used in exercise provided that (a)
the working muscles have sufficient mitochondria to meet energy requirements, (b) sufficient
oxygen is supplied to the mitochondria, and (c) enzymes or intermediate products do not limit
the rate of energy flux through the Kreb’s cycle and respiratory chain – the bioenergetic
pathways that produce ATP within the mitochondria.
The pathway for oxygen transport involves three main structures; the lungs, the circulation, and
the muscle. Oxygen follows a simple linear pathway without branches. Respiration is a regulated
process matched to the instantaneous demands of aerobic metabolism: as muscle ATP
consumption increases, O2 demand is increased proportionally (27). Increases in oxygen
transport that occur during exercise are brought about as a result of an increase in ventilation and
uptake of oxygen into the blood, an increased cardiac output and O2 transport by the blood, and
an increased extraction of O2 by the muscle due to increased O2 metabolism in the mitochondria.
Respiration is a limited function, and the limit of the maximal rate of oxygen that can be
consumed to produce energy in the muscle is termed VO2max. Any additional energy
requirements beyond that intensity will be fulfilled via anaerobic metabolism. VO2max is higher
in athletes than non-athletes, and to an extent is malleable and can be elevated by training (27).
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Further, the pathway for oxygen transport from the environment to the mitochondria in the
skeletal muscle cells is linear. The actual process of respiration is the integrated function
involving the coordinated action of all of the structures that make up the pathway for delivery of
O2 from the lungs to the respiratory chain enzymes in the mitochondria of the muscle cell (27). A
metaphor for understanding the respiratory pathway can be developed using an electric circuit as
the example. In this case the individual steps can be viewed as resistors in series, and the total
resistance can be estimated by the difference in arterial and venous O2 levels. The oxygen flux
(VO2) can be thought of as current, and total oxygen transport (cardiac output) as voltage. Since
voltage = current x resistance, the equation becomes VO2 = cardiac output x (arterial-venous O2
difference). The relative contribution of the individual steps in the respiratory pathway has been
a subject of some debate, however, using the above electrical circuit model, it has been shown
that for humans exercising in normoxia, approximately 75% of VO2max is set by central O2
transport and the remaining 25% by the periphery (28). Thus, it is now generally accepted that it
is the integrated, interactive steps in the respiratory pathway that help set VO2max (27).
In human muscle mitochondria, a complex biochemical process known as oxidative
phosphorylation is used to resynthesize ATP. Mitochondria are energy-generating organelles in
the muscle fibres that contain a system of enzymes, coenzymes, and activators that carry on the
oxidation of nutrients and release ATP for use in aerobic work. Oxidative phosphorylation
consists of pathways that include the Krebs (also known as the citric acid) cycle (see figure 6)
and the electron transport chain. The processes combine ADP and Pi through biochemical steps
in the presence of oxygen to synthesize ATP. Both carbohydrates (glycogen and glucose) and
fats (triglycerides and fatty acids) provide molecules that are used in oxidative phosphorylation.
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The system is highly efficient; the energy yield from the metabolism of glucose as the substrate
is 36 ATP molecules in conditions of adequate oxygen supply (18 times the yield from the
anaerobic system). Fats are an important energy source for athletic events that require large
outputs of energy over a long period of time. For example, the oxidation of an 18-carbon fatty
acid molecule produces 147 molecules of ATP. Water and carbon dioxide are given off as byproducts of this reaction. Fats are an ideal molecule for storage of energy (each gram of lipid
yeilds approximately 9.4 kilocalories of energy, more than twice the amount found in
carbohydrates or proteins. A normal person has enough energy stored as fats to run hundreds of
miles, but only enough stored carbohydrate to run about 20 miles! In addition to the efficient
provision of energy for muscular contraction, the aerobic system is used to re-establish cellular
homeostasis in muscle tissue after intensive exercise bouts. More specifically, removal of lactic
acid from muscle tissue is accomplished largely via conversion of lactate back to pyruvate and
then subsequent processing of pyruvate in the Krebs cycle. The lactic acid, once produced in
type II muscle fibres, is actively transported into the blood and into type I fibres where lactate
can be metabolized back to pyruvic acid.
<<Insert Figure 6 near here>>
Endurance exercise is the method of training that is most effective for eliciting adaptations in the
aerobic oxidative energy system. It consists of sustained low to moderate intensity activity (50 –
75% of maximum heart rate) of long duration, typically in excess of 20 minutes and as long as
several hours. Aerobic endurance exercise stimulates positive adaptations throughout the entire
cardiovascular system, making it an excellent intervention for improving health and performance
and for preventing or even treating various diseases, particularly obesity (29) and Type II
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diabetes (30). The major adaptations that occur in the human body with aerobic endurance
training are summarized in Figure 7.
<<Insert Figure 7 near here>>
Endurance training increases the maximal aerobic power of a sedentary individual by 15-25%
regardless of age. Genetics plays a large role in determining the rate of adaptation, with some
individuals adapting quickly and others more slowly (31). Endurance training has many effects
on aerobic metabolism and related physiological functions:
1. Increased cardiac output. The increase in cardiac output may arise due to an increase in
the size of the heart cavities (ventricles and atria) as well as an increase in the
contractility of the walls of the heart (32).
2. Increased vascularization (number of blood vessels and capillaries) within skeletal
muscle (26) and heart muscle (33). Increased capillarization is a benefit as it allows for a
greater surface area and reduced distance between the blood and the surrounding tissues,
thus increasing diffusion capacity of oxygen and carbon dioxide, as well as easing the
transport of nutrients to cells (34).
3. Decreased blood pressure (35).
4. Increased total blood volume (36) and the number and total volume of red blood cells
through stimulation of erythropoiesis (formation of new red blood cells) in the bone
marrow (37).
5. Increased number and size of mitochondria within the muscle fibres (38) (39).
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6. Increased activity of aerobic enzymes such as AMP kinase (40) and Krebs cycle enzymes
(38) which can be observed as an increased arterial-venous O2 difference, and
7. Preferential use of fats over glycogen during exercise (41).
In summary, aerobic endurance training stimulates many positive adaptations in aerobic
oxidative metabolism and the cardiovascular system as a whole. Optimal health and performance
depend upon these adaptations. It is important that health professionals understand these
adaptations in order to be able to impart this knowledge to the general population and to
encourage individuals to adopt lifestyles that will improve their health and quality of life.
Summary of Energy Systems Physiology
The function of muscles is to convert chemical energy from food into mechanical energy,
allowing individuals to perform muscular work. Fats, carbohydrates and proteins are the basic
interrelated fuel sources that are available to muscles to perform this function. High energy
phosphates contribute anaerobic energy to the muscle system. Very high power outputs can be
produced on demand, but these outputs can only be maintained for very short durations. Small
amounts of blood glucose and large amounts of muscle glycogen can also supply energy rapidly.
High power outputs can be maintained in this fashion through anaerobic glycolysis accompanied
by lactic acid production. Lower power outputs for sustained periods of time can be maintained
by aerobic oxidation of glycogen with limited production of lactate. Fuel stored as fat is also
available to the mitochondria for oxidation and is limited to slow production of ATP at low
power outputs for sustained periods of time.
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Figure Captions
Figure 1. Contributions of the three energy systems to activities of different durations and power
outputs.
Figure 2. An electron micrograph of the inside of a muscle fibre. The actin and myosin
filaments, mitochondria (white arrows) and lipid droplets (black arrows) are clearly visible
(Images courtesy of M. Tarnopolski).
Figure 3. A general representation of aerobic, anaerobic and high energy phosphate bioenergetic
pathways.
Figure 4. The steps of anaerobic glycolysis. Adapted from McArdle W D et al., 2007 (14).
Figure 5. Representation of lactate transport metabolism in different muscle fibre types. Adapted
from (20).
Figure 6. A graphical representation of the steps in the Krebs cycle. Krebs cycle substrates are
presented in black, enzymes are indicated in green, and metabolic by-products in blue.
Figure 7. The oxygen transport pathway and related adaptations to aerobic endurance training.
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References
1. Abernethy P J, Thayer R, Taylor A W. Acute and chronic responses of skeletal muscle to
endurance and sprint exercise. A review. Sports Med 1990 Dec; 10(6):365-89.
2. Morton R H, Hodgson D J. The relationship between power output and endurance: A brief
review. Eur J Appl Physiol Occup Physiol 1996; 73(6):491-502.
3. Hargreaves M. Skeletal muscle metabolism during exercise in humans. Clin Exp Pharmacol
Physiol 2000 Mar; 27(3):225-8.
4. Wilmore J H, Costill D L., editors. Physiology of sport and exercise. 3rd Edition ed. Human
Kinetics; 2004.
5. Hultman E, Bergstrom J, Anderson N M. Breakdown and resynthesis of phosphorylcreatine
and adenosine triphosphate in connection with muscular work in man. Scand J Clin Lab Invest
1967; 19(1):56-66.
6. Homma T, Hamaoka T, Sako T, Murakami M, Esaki K, Kime R, et al. Muscle oxidative
metabolism accelerates with mild acidosis during incremental intermittent isometric plantar
flexion exercise. Dyn Med 2005 Feb 20; 4(1):2.
7. Terjung R L, Clarkson P, Eichner E R, Greenhaff P L, Hespel P J, Israel R G, et al. American
college of sports medicine roundtable. the physiological and health effects of oral creatine
supplementation. Med Sci Sports Exerc 2000 Mar; 32(3):706-17.
8. MacDougall J D, Ward G R, Sale D G, Sutton J R. Biochemical adaptation of human skeletal
muscle to heavy resistance training and immobilization. J Appl Physiol 1977 Oct; 43(4):700-3.
Page 20 of 33
Bioenergetic provision of energy for muscular activity
9. Dawson B, Fitzsimons M, Green S, Goodman C, Carey M, Cole K. Changes in performance,
muscle metabolites, enzymes and fibre types after short sprint training. Eur J Appl Physiol
Occup Physiol 1998 Jul; 78(2):163-9.
10. Costill D L, Coyle E F, Fink W F, Lesmes G R, Witzmann F A. Adaptations in skeletal
muscle following strength training. J Appl Physiol 1979 Jan; 46(1):96-9.
11. Mohr M, Krustrup P, Nielsen J J, Nybo L, Rasmussen M K, Juel C, et al. Effect of two
different intense training regimes on skeletal muscle ion transport proteins and fatigue
development. Am J Physiol Regul Integr Comp Physiol 2006 Dec 28.
12. Vikne H, Refsnes P E, Ekmark M, Medbo J I, Gundersen V, Gundersen K. Muscular
performance after concentric and eccentric exercise in trained men. Med Sci Sports Exerc 2006
Oct; 38(10):1770-81.
13. Spriet LL, Howlett RA, Heigenhauser GJ. An enzymatic approach to lactate production in
human skeletal muscle during exercise. Med Sci Sports Exerc 2000 Apr; 32(4):756-63.
14. McArdle W D, Katch F L, Katch V L. Exercise physiology: Energy, nutrition and human
performance. 5th Edition ed. McArdle W D, Katch F L, Katch V L, editors. Lippincott Williams
& Wilkins; 2007.
15. di Prampero P E, Ferretti G. The energetics of anaerobic muscle metabolism: A reappraisal
of older and recent concepts. Respir Physiol 1999 Dec 1; 118(2-3):103-15.
16. Myers J, Ashley E. Dangerous curves. A perspective on exercise, lactate, and the anaerobic
threshold. Chest 1997 Mar; 111(3):787-95.
Page 21 of 33
Bioenergetic provision of energy for muscular activity
17. Brooks G A. Current concepts in lactate exchange. Med Sci Sports Exerc 1991 Aug;
23(8):895-906.
18. Svedahl K, MacIntosh B R. Anaerobic threshold: The concept and methods of measurement.
Can J Appl Physiol 2003 Apr; 28(2):299-323.
19. Noakes T D. Physiological models to understand exercise fatigue and the adaptations that
predict or enhance athletic performance. Scand J Med Sci Sports 2000 Jun; 10(3):123-45.
20. Bonen A. Lactate transporters (MCT proteins) in heart and skeletal muscles. Med Sci Sports
Exerc 2000 Apr; 32(4):778-89.
21. Laursen P B, Jenkins D G. The scientific basis for high-intensity interval training:
Optimising training programmes and maximising performance in highly trained endurance
athletes. Sports Med 2002; 32(1):53-73.
22. Parkhouse W S, McKenzie D C. Possible contribution of skeletal muscle buffers to enhanced
anaerobic performance: A brief review. Med Sci Sports Exerc 1984 Aug; 16(4):328-38.
23. Juel C. Current aspects of lactate exchange: Lactate/H+ transport in human skeletal muscle.
Eur J Appl Physiol 2001 Nov; 86(1):12-6.
24. Tomlin D L, Wenger H A. The relationship between aerobic fitness and recovery from high
intensity intermittent exercise. Sports Med 2001; 31(1):1-11.
25. Delp M D. Differential effects of training on the control of skeletal muscle perfusion. Med
Sci Sports Exerc 1998 Mar; 30(3):361-74.
Page 22 of 33
Bioenergetic provision of energy for muscular activity
26. Xu F, Rhodes E C. Oxygen uptake kinetics during exercise. Sports Med 1999 May;
27(5):313-27.
27. Hoppeler H, Weibel E R. Limits for oxygen and substrate transport in mammals. J Exp Biol
1998 Apr; 201(Pt 8):1051-64.
28. di Prampero P E. Metabolic and circulatory limitations to VO2 max at the whole animal
level. J Exp Biol 1985 Mar; 115:319-31.
29. Bonen A, Dohm G L, van Loon L J. Lipid metabolism, exercise and insulin action. Essays
Biochem 2006; 42:47-59.
30. Thomas D E, Elliott E J, Naughton G A. Exercise for type 2 diabetes mellitus. Cochrane
Database Syst Rev 2006 Jul 19; 3:CD002968.
31. Macarthur D G, North K N. Genes and human elite athletic performance. Hum Genet 2005
Apr; 116(5):331-9.
32. Cox M L, Bennett J B,3rd, Dudley G A. Exercise training-induced alterations of cardiac
morphology. J Appl Physiol 1986 Sep; 61(3):926-31.
33. Gielen S, Hambrecht R. Effects of exercise training on vascular function and myocardial
perfusion. Cardiol Clin 2001 Aug; 19(3):357-68.
34. Suter E, Hoppeler H, Claassen H, Billeter R, Aebi U, Horber F, et al. Ultrastructural
modification of human skeletal muscle tissue with 6-month moderate-intensity exercise training.
Int J Sports Med 1995 Apr; 16(3):160-6.
Page 23 of 33
Bioenergetic provision of energy for muscular activity
35. Cox K L. Exercise and blood pressure: Applying findings from the laboratory to the
community setting. Clin Exp Pharmacol Physiol 2006 Sep; 33(9):868-71.
36. Kubukeli Z N, Noakes T D, Dennis S C. Training techniques to improve endurance exercise
performances. Sports Med 2002; 32(8):489-509.
37. Szygula Z. Erythrocytic system under the influence of physical exercise and training. Sports
Med 1990 Sep; 10(3):181-97.
38. Taylor A W, Bachman L. The effects of endurance training on muscle fibre types and
enzyme activities. Can J Appl Physiol 1999 Feb; 24(1):41-53.
39. Hoppeler H, Fluck M. Plasticity of skeletal muscle mitochondria: Structure and function.
Med Sci Sports Exerc 2003 Jan; 35(1):95-104.
40. Hardie D G. AMP-activated protein kinase: A key system mediating metabolic responses to
exercise. Med Sci Sports Exerc 2004 Jan; 36(1):28-34.
41. Jeukendrup A E. Modulation of carbohydrate and fat utilization by diet, exercise and
environment. Biochem Soc Trans 2003 Dec; 31(Pt 6):1270-3.
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Bioenergetic provision of energy for muscular activity
Table 1.
Table 1. Functional Characteristics of Human Muscle Fibres
Fibre Type
Alternate name
Primary source af ATP
Myosin- ATPase activity
Glycolytic enzyme content
Glycogen content
Number of mitochondria
Myoglobin content
Capillary density
Speed of contraction
Rate of fatigue
Type I
Slow Oxidative
Aerobic Oxidation
Low
Low
Low
High
High
High
Slow
Slow
Type IIa
Fast Oxidative Glycolytic
Aerobic Oxidation &
Anaerobic Glycolysis
High
Intermediate
Intermediate
High
Intermediate
Intermediate
Fast
Intermediate
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Type IIb
Fast Glycolytic
Anaerobic Glycolysis
High
High
High
Low
Low
Low
Fast
Fast
Bioenergetic provision of energy for muscular activity
Table 2.
Table 2. Characteristics of the 3 energy systems
Characteristic
Fuel source(s)
Enzyme sytem used in breakdown
Muscle fibre type(s) recruited
Power output requirement
Metbolic byproducts
maximum rate of ATP production
(mmol/min)
Time to maximal ATP production
Maintenance time of maximal ATP
production
Time to exhaustion of system
Ultimate limiting factor(s)
Time for total recovery (sec)
Time for one half recovery (sec)
Relative % ATP contribution to efforts
of 10 sec
Relative % ATP contribution to efforts
of 30 sec
Relative % ATP contribution to efforts
of 2 min
Relative % ATP contribution to efforts
of 10 min
High energy phosphate
stored ATP, phosphocreatine
(PCr)
ATPase
Type I, Type IIa, Type IIb
high
ADP, P, Cr
3.6
Anaerobic glycolytic
stored glycogen, blood glucose
Aerobic oxidative
glycogen, glucose, fats, proteins
HK, PFK, LDH, PDH, others
Type I, Type IIa, Type IIb
moderate - high
lactic acid
1.6
CS, MDH, SDH, others
Type I, Type IIa
low - moderate
CO2, H2O
1
5-10 sec
20-30 sec
2-3 min
3 min
1 sec
6-10 sec
12-15 sec
Depletion of ATP / PCr stores
45-90 sec
Lactic acid accumulation
3 min
20-30 sec
1-2 hr
15-20 min
50
35
15
15
65
20
4
46
50
1
9
90
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theoretically unlimited
Depletion of carbohydrate
stores, insufficient oxygen, heat
accumulation
30-60 min
5-10 min
Bioenergetic provision of energy for muscular activity
Figure 1.
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Bioenergetic provision of energy for muscular activity
Figure 2.
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Bioenergetic provision of energy for muscular activity
Figure 3.
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Bioenergetic provision of energy for muscular activity
Figure 4.
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Bioenergetic provision of energy for muscular activity
Figure 5.
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Bioenergetic provision of energy for muscular activity
Figure 6.
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Bioenergetic provision of energy for muscular activity
Figure 7.
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