Carbohydrate Metabolism in Exercise

Chapter 6
Carbohydrate Metabolism in Exercise
ERIC HULTMAN AND PAUL L. GREENHAFF
Introduction
During exercise, the energy demands of muscle
contraction will fluctuate enormously. For
muscle contraction to occur, chemical energy
stored in the form of adenosine triphosphate
(ATP) must be converted into mechanical energy
at rates appropriate to the needs of the muscle.
However, the muscle store of ATP is relatively
small and therefore for exercise to continue
beyond a few seconds ATP must be resynthesized from phosphocreatine, carbohydrate and
fat. It is generally accepted that carbohydrate is
the major substrate for ATP resynthesis during
intense exercise. The carbohydrate stores of the
body are principally located in skeletal muscle
and liver, with small amounts also being found
in the form of circulating glucose. The amount
of energy stored as glycogen amounts to approximately 6000 kJ (1430 kcal) and 1500 kJ
(360 kcal) in muscle and liver, respectively, which
is very small compared with the body store of triacylglycerol (340 MJ, 81 200 kcal), the alternative
fuel for ATP resynthesis. Triacylglycerol is the
preferred substrate for energy production in
resting muscle and can cover the energy
demands of exercise up to 50% of maximal
oxygen consumption. At higher exercise intensities, the relative contribution of fat to total
energy production falls and carbohydrate oxidation increases, such that carbohydrate is the
sole fuel oxidized at the highest exercise intensities. This is due to an increasing recruitment of
the glycolytic type II muscle fibres and an activa-
tion of glycolytic enzymes when ATP turnover
rate is increased. The maximal rate of ATP production from lipid is lower than that of carbohydrate. In addition, the ATP yield per mole of
oxygen utilized is lower for lipid compared with
carbohydrate. In contrast with lipid, carbohydrate can be metabolized anaerobically via glycolysis. The lactate accumulation that occurs
almost instantaneously at the onset of contraction demonstrates that the activation of this
pathway is extremely rapid. It should be noted
that the anaerobic utilization of carbohydrate
will be indispensable during the transition from
rest to steady-state exercise and during maximal
exercise. Furthermore, the relatively small store
of body carbohydrate will limit exercise performance during prolonged intense exercise due to
the depletion of muscle and liver glycogen
stores.
The body store and maximal rates of ATP
resynthesis from phosphocreatine, carbohydrate
and lipid are shown in Table 6.1.
Regulation of muscle carbohydrate
utilization during exercise
Glycogenolysis is the hydrolysis of muscle
glycogen to glucose-1-phosphate, which is
transformed to glucose-6-phosphate via a
phosphoglucomutase reaction. The glucose-6phosphate formed, together with that derived
from the phosphorylation of blood glucose by
hexokinase at the muscle cell membrane, enters
the glycolytic pathway which is a series of
85
86
nutrition and exercise
Table 6.1 The amounts of substrate available and the maximal rates of energy production from phosphocreatine,
carbohydrate and lipid in a 70-kg man (estimated muscle mass, 28 kg).
ATP, PCr Æ ADP, Cr
Muscle glycogen Æ Lactate
Muscle glycogen Æ CO2
Liver glycogen Æ CO2
Fatty acids Æ CO2
Amount available
(mol)
Production rate
(mol · min-1)
0.67
6.70*
84
19
4000*
4.40
2.35
0.85–1.14
0.37
0.40
* These pathways of substrate utilization will not be fully utilized during exercise.
reactions involved in the degradation of glucose6-phosphate to pyruvate.
Glycogenolysis
The integrative nature of energy metabolism
ensures that the activation of muscle contraction
by Ca2+ and the accumulation of the products of
ATP and phosphocreatinine (PCr) hydrolysis
(ADP, AMP, IMP, NH3 and Pi) act as stimulators
of glycogenolysis, and in this way attempt to
match the ATP production to the demand. The
control of glycogenolysis during muscle contraction is a highly complex mechanism which can
no longer be considered to centre only around
the degree of Ca2+ induced transformation of less
active glycogen phosphorylase b to the more
active a form, as is suggested in many textbooks.
For some time it has been known that
glycogenolysis can proceed at a negligible rate,
despite almost total transformation of phosphorylase to the a form; for example, following
adrenaline infusion (Chasiotis et al. 1983). Conversely, an increase in glycogenolytic rate has
been observed during circulatory occlusion,
despite a relatively low mole fraction of the phosphorylase a form (Chasiotis 1983). From this and
other related work, it was concluded that inorganic phosphate (Pi) accumulation arising from
ATP and PCr hydrolysis played a key role in the
regulation of the glycogenolytic activity of
phosphorylase a, and by doing so served as a link
between the energy demand of the contraction and the rate of carbohydrate utilization
(Chasiotis 1983). However, the findings that high
rates of glycogenolysis can occur within 2 s of the
onset of muscle contraction in conjunction with
only a small increase in Pi and, more recently, that
glycogenolysis can proceed at a low rate despite
a high phosphorylase a form and Pi concentration, suggest that factors other than the degree of
Ca2+ induced phosphorylase transformation and
Pi availability are involved in the regulation of
glycogenolysis (Ren & Hultman 1989, 1990).
Classically, both inosine monophosphate
(IMP) and adenosine monophosphate (AMP)
have been associated with the regulation of
glycogenolysis during exercise (Lowry et al. 1964;
Aragon et al. 1980). IMP is thought to exert its
effect by increasing the activity of phosphorylase b during contraction (the apparent Km
(Michaeli’s constant) of phosphorylase b for IMP
is about 1.2 mmol · l–1 intracellular water). AMP
has also been shown to increase the activity of
phosphorylase b, but it is thought to require an
unphysiological accumulation of free AMP to do
so (the apparent Km of phosphorylase b for AMP
is about 1.0 mmol · l–1 intracellular water). In vitro
experiments have demonstrated that AMP can
bring about a more marked effect on glycogenolysis by increasing the glycogenolytic activity of
phosphorylase a (Lowry et al. 1964). Because 90%
or more of the total cell content of AMP may be
bound to cell proteins in vivo, it has in the past
been questioned whether the increase in free
AMP during contraction is of a sufficient magnitude to affect the kinetics of phosphorylase a.
More recent work, however, demonstrates that a
carbohydrate metabolism in exercise
small increase in AMP concentration (10 mmol ·
l–1) can markedly increase the in vitro activity of
phosphorylase a (Ren & Hultman 1990). Furthermore, in vivo evidence demonstrating a close
relationship between muscle ATP turnover and
glycogen utilization suggests that an exerciseinduced increase in free AMP and inorganic
phosphate may be the key regulators of glycogen
degradation during muscle contraction (Ren &
Hultman 1990).
Glycolysis
From the preceding discussions it can be seen
that the rate of glycogenolysis is determined
by the activity of glycogen phosphorylase.
However, it is the activity of phosphofructokinase (PFK) that dictates the overall rate of glycolytic flux (Tornheim & Lowenstein 1976). PFK
acts as a gate to the flow of hexose units through
glycolysis and there is no other enzyme subsequent to PFK that is capable of matching flux rate
with the physiological demand for ATP. Stimulation of glycogen phosphorylase by adrenaline
and/or exercise results in the accumulation of
glucose-6-phosphate demonstrating that PFK is
the rate limiting step in the degradation of
hexose units to pyruvate (Richter et al. 1986).
ATP is known to be the most potent allosteric
inhibitor of PFK. The most important activators
or deinhibitors of PFK are adenosine diphosphate (ADP), AMP, Pi, fructose-6-phosphate,
glucose 1–6 bisphosphate, fructose 1–6 and 2–6
bisphosphates and, under extreme conditions,
ammonia. Removal of the ATP-mediated inhibition of PFK during contraction, together with the
accumulation of the positive modulators of PFK,
is responsible for the increase in flux through the
enzyme during exercise and thereby is responsible for matching glycolytic flux with the energy
demand of contraction.
Hydrogen ion and citrate accumulation during
contraction have been suggested to be capable
of decreasing the activity of PFK and, thereby,
the rate of glycolysis during intense exercise.
However, it is now generally accepted that the
extent of this inhibition of glycolysis during exer-
87
cise is overcome in the in vivo situation by the
accumulation of PFK activators (Spriet et al.
1987).
Pyruvate oxidation
It has been accepted for some time that the rate
limiting step in carbohydrate oxidation is the
decarboxylation of pyruvate to acetyl-coenzyme
A (CoA), which is controlled by the pyruvate
dehydrogenase complex (PDC), and is essentially an irreversible reaction committing pyruvate to entry into the tricarboxylic acid (TCA)
cycle and oxidation (Wieland 1983). The PDC is a
conglomerate of three enzymes located within
the inner mitochondrial membrane. Adding to
its complexity, PDC also has two regulatory
enzymes: a phosphatase and a kinase which
regulate an activation–inactivation cycle. Increased ratios of ATP/ADP, acetyl-CoA/CoA
and NADH/NAD+ activate the kinase, resulting
in the inactivation of the enzyme. Conversely,
decreases in the above ratios and the presence
of pyruvate will inactivate the kinase, whilst
increases in calcium will activate the phosphatase, together resulting in the activation of
PDC. Thus, it can be seen that the increases in
calcium and pyruvate availability at the onset of
contraction will result in the rapid activation of
PDC. These factors, together with the subsequent
decrease in the ATP/ADP ratio as contraction
continues, will result in continued flux through
the reaction (Constantin-Teodosiu et al. 1991).
Following decarboxylation of pyruvate by the
PDC reaction, acetyl-CoA enters the TCA cycle,
resulting in the formation of citrate, in a reaction
catalysed by citrate synthase. The rate of flux
through the TCA cycle is thought to be regulated
by citrate synthase, isocitrate dehydrogenase,
and a-ketoglutarate dehydrogenase. The activity
of these enzymes is controlled by the mitochondrial ratios of ATP/ADP and NADH/NAD+.
Good agreement has been found between the
maximal activity of a-ketoglutarate dehydrogenase and flux through PDC and the TCA cycle.
The last stage in pyruvate oxidation involves
NADH and FADH generated in the TCA cycle
88
nutrition and exercise
entering the electron transport chain. In the electron transport chain, NADH and FADH are
oxidized and the energy generated is used to
rephosphorylate ADP to ATP. The rate of flux
through the electron transport chain will be regulated by the availability of NADH, oxygen and
ADP (Chance & Williams 1955). Finally, the
translocation of ATP and ADP across the mitochondrial membrane is thought to be effected by
creatine by way of the mitochondrial creatine
kinase reaction (Moreadith & Jacobus 1982),
thereby linking mitochondrial ATP production to
the ATPase activity in the contractile system.
Lactate production
Considerable controversy exists concerning the
mechanism responsible for lactate accumulation
during intense muscle contraction. The most
widely accepted theory attributes this to a high
rate of energy demand coupled with an inadequate oxygen supply. In short, when tissue
oxygen supply begins to limit oxidative ATP production, resulting in the accumulation of mitochondrial and cytosolic NADH, flux through
glycolysis and a high cytosolic NAD+/NADH
ratio are maintained by the reduction of pyruvate
to lactate. However, it has been suggested that
the reduction in mitochondrial redox state
during contraction is insignificant, thereby indicating that reduced oxygen availability is not the
only cause of lactate accumulation during contraction (Graham & Saltin 1989). In addition,
there are data to indicate that it is the activation
of the PDC and the rate of acetyl group production, and not oxygen availability, which primarily regulates lactate production during intense
muscle contraction (Timmons et al. 1996). Furthermore, it has also been shown that for any
given workload, lactate accumulation can be
significantly altered by pre-exercise dietary
manipulation (Jansson 1980; Putman et al. 1993).
Taken together, these findings suggest that an
imbalance between pyruvate formation and
decarboxylation to acetyl-CoA will dictate the
extent of lactate formation during exercise as
seen, for example, during the transition period
from rest to steady-state exercise.
Glycogen utilization with respect to
exercise intensity
Maximal exercise
During submaximal (steady-state) exercise, ATP
resynthesis can be adequately achieved by oxidative combustion of fat and carbohydrate stores.
However, during high-intensity (non-steady
state) exercise, the relatively slow activation and
rate of energy delivery of oxidative phosphorylation cannot meet the energy requirements of
contraction. In this situation, anaerobic energy
delivery is essential for contraction to continue.
Typically, oxidative energy delivery requires
several minutes to reach a steady state, due principally to the number and complexity of the reactions involved. Once achieved, the maximal rate
of ATP production is in the region of approximately 2.5 mmol · kg–1 dry matter (dm) · s–1. On
the other hand, anaerobic energy delivery is
restricted to the cytosol, its activation is almost
instantaneous and it can deliver ATP at a rate in
excess of 11 mmol · kg–1 dm · s–1. The downside,
however, is that this can be maintained for only a
few seconds before beginning to decline. Of
course, oxidative and anaerobic ATP resynthesis
should not be considered to function independently of one another. It has been demonstrated
that as the duration of exercise increases, the
contribution from anaerobic energy delivery
decreases, whilst that from aerobic is seen to
increase.
Figure 6.1 shows that maximal rates of ATP
resynthesis from PCr and glycogen degradation
can only be maintained for short time periods
during maximal contraction in man (Hultman
et al. 1991). The rate of PCr degradation is at its
maximum immediately after the initiation of
contraction and begins to decline after only 1.3 s.
Conversely, the corresponding rate of glycolysis
does not peak until after approximately 5 s of
contraction and does not begin to decline until
carbohydrate metabolism in exercise
89
10
Fig. 6.1 Rates of anaerobic ATP
formation from phosphocreatine
and glycolysis during maximal
intermittent electrically evoked
isometric contraction in man (see
Hultman et al. 1991). Note that the
reference base for the muscle data
in the figures and text is dry
muscle. This is because the muscle
samples were freeze-dried prior to
biochemical analysis. To convert to
wet weight, values should be
divided by 4.3. This assumes 1 kg
of wet muscle contains 70 ml of
extracellular water and 700 ml of
intracellular water. ,
phosphocreatine; , glycolysis.
ATP production (mmol.kg–1 muscle.s–1)
8
6
4
2
0
0–1.3
after 20 s of contraction. This suggests that the
rapid utilization of PCr may buffer the momentary lag in energy provision from glycolysis, and
that the contribution of the latter to ATP resynthesis rises as exercise duration increases and
PCr availability declines. This point exemplifies
the critical importance of PCr at the onset of contraction. Without this large hydrolysis of PCr, it is
likely that muscle force production would almost
instantaneously be impaired, which is indeed the
case in muscles in which the PCr store has been
replaced with a Cr analogue (Meyer et al. 1986). It
is also important to note that ultimately there is a
progressive decline in the rate of ATP resynthesis
from both substrates during this type of exercise.
For example, during the last 10 s of exercise
depicted in Fig. 6.1, the rate of ATP production
from PCr hydrolysis had declined to approximately 2% of the peak rate. Similarly, the corresponding rate of ATP resynthesis from glycogen
hydrolysis had fallen to approximately 40%.
The above example concerns exercise of
maximal intensity lasting about 30 s. However,
0–2.6
0–5
0–10
10–20
20–30
Exercise time (s)
non-steady-state exercise, albeit less intense, can
be sustained for durations approaching 5–15 min
before fatigue is evident. Under these conditions,
carbohydrate oxidation can make a major contribution to ATP production and therefore its
importance should not be underestimated.
It has been demonstrated that during 3.2 min
of fatiguing exercise, oxidative phosphorylation
can contribute as much as 55% of total energy
production (Bangsbo et al. 1990). This indicates
the importance of substrate oxidation during
high-intensity exercise, a point which is often
overlooked. Under these conditions, muscle
glycogen is the principal fuel utilized as muscle
glucose uptake is inhibited by glucose 6phosphate accumulation and adipose tissue
lipolysis is inhibited by lactate accumulation.
Submaximal exercise
The term submaximal exercise is typically used to
define exercise intensities which can be sustained
for durations falling between 30 and 180 min.
90
nutrition and exercise
In practice, this is usually exercise intensities
between 60% and 85% of maximal oxygen consumption. Continuous exercise of any longer
duration (i.e. an intensity of less than 60% of
maximal oxygen consumption) is probably not
limited by substrate availability and, providing
adequate hydration is maintained, can probably
be sustained for several hours or even days!
Unlike maximal intensity exercise, the rate of
muscle ATP production required during prolonged exercise is relatively low (< 2.5 mmol · kg–1
dm · s–1) and therefore PCr, carbohydrate and fat
can all contribute to ATP resynthesis. However,
carbohydrate is without question the most
important fuel source.
It can be calculated that the maximum rate
of ATP production from carbohydrate oxidation
will be approximately 2.0–2.8 mmol · kg–1
dm · s–1 (based upon a maximum oxygen consumption of 3–4 l · min–1), which corresponds to
a glycogen utilization rate of approximately
4 mmol · kg–1 dm · min–1. Therefore, it can be seen
that carbohydrate could meet the energy requirements of prolonged exercise. However, because
the muscle store of glycogen is in the region of
350 mmol · kg–1 dm, under normal conditions, it
can be calculated that it could only sustain in the
region of 80 min of exercise. This was demonstrated in the 1960s by Bergström and Hultman
(1967). The authors also demonstrated that if the
glycogen store of muscle was increased by
dietary means, exercise duration increased in
parallel (Bergström et al. 1967). Of course, carbohydrate is also delivered to skeletal muscle from
hepatic stores in the form of blood glucose and
this can generate ATP at a maximum rate of
approximately 1 mmol · kg–1 dm · s–1.
The majority of hepatic glucose release during
exercise (1.5–5.5 mmol · min–1) is utilized by
skeletal muscle. Only 0.5 mmol · min–1 is utilized
by extramuscular tissue during exercise. Muscle
glucose utilization is dependent on glucose
supply, transport and metabolism. If blood
glucose is unchanged, as in the majority of exercise conditions, glucose supply to muscle is dictated by muscle blood flow, which increases
linearly with exercise intensity and can increase
by 20-fold from rest to maximal exercise. The
increase in muscle glucose delivery as a result of
the exercise- mediated increase in blood flow is
probably more important for muscle glucose
uptake during exercise than the insulin and contraction-induced increase in membrane glucose
transport capacity (see Richter & Hespel 1996).
As exercise continues, plasma insulin concentration declines, which facilitates hepatic glucose
release and reduces glucose utilization by extramuscular tissue. However, insulin supply to
muscle probably remains elevated above basal
supply due to the contraction-induced elevation
in muscle blood flow.
Hexokinase is responsible for the phosphorylation of glucose by ATP when it enters the
muscle cell. The enzyme is allosterically inhibited by glucose-6-phosphate, the product of the
hexokinase reaction and an intermediate of glycolysis. Thus, during short-term high-intensity
exercise and at the onset of prolonged submaximal exercise, glucose phosphorylation by
hexokinase will be inhibited by glucose-6phosphate accumulation. This will increase the
concentration of glucose in the extra- and intracellular water and will contribute to the increase
in blood glucose observed during high-intensity
exercise. However, as submaximal exercise
continues, the decline in muscle glucose-6phosphate results in an increase in glucose
phosphorylation.
In comparison with muscle glycogen metabolism, relatively little is known about the interaction between exercise and hepatic glycogen
metabolism in man. This is not because of a lack of
interest but because of the invasive nature of the
liver biopsy technique. The few studies that have
been performed in healthy volunteers using this
technique have demonstrated that the rate of
liver glucose release in the postabsorptive state is
in the region of 0.8 mmol glucose · min–1, which
is sufficient to meet the carbohydrate demands
of the brain and obligatory glucolytic tissues.
Approximately 60% of this release (0.5 mmol ·
min–1) is derived from liver glycogen stores and
the remainder is synthesized by gluconeogenesis
in the liver using lactate, pyruvate, glycerol and
carbohydrate metabolism in exercise
91
6
85%
4
75%
3
55%
2
30%
1
0
amino acids as substrates (Hultman & Nilson
1971; Nilsson & Hultman 1973).
The rate of hepatic glucose release during exercise in the postabsorptive state has been shown
to be mainly a function of exercise intensity (Fig.
6.2) (Hultman 1967; Wahren et al. 1971; Ahlborg et
al. 1974; Ahlborg & Felig 1982). The uptake of
gluconeogenic precursors by the liver is only
marginally increased during the initial 40 min of
submaximal exercise but increases further as
exercise continues (Ahlborg et al. 1974). Most
(more than 90%) of the glucose release is derived
from liver glycogenolysis resulting in a decline
and ultimately depletion of liver glycogen stores.
Direct measurements of liver glycogen concentration in the postabsorptive state and following
60 min of exercise at 75% of maximal oxygen consumption showed a 50% decrease in the liver
glycogen concentration with exercise (Fig. 6.3).
This corresponded to a glycogen degradation
rate of 4.2 mmol · min–1 (assuming 1.8 kg of liver)
and suggested that the liver glycogen store
would have been depleted within 120 min of
exercise at this intensity.
The exact mechanisms responsible for the
regulation of liver glucose release at the onset
and during exercise are still unresolved.
However, it is known that the decline in blood
0
(rest)
10
20
30
40
120
180
240
Work time (min)
400
Liver glycogen (mmol.kg–1 wet wt)
Fig. 6.2 Hepatic glucose release
during exercise at 30%, 55%, 75%
and 85% of maximal oxygen
consumption in men. From
Ahlborg et al. (1974), Ahlborg and
Felig (1982), Wahren et al. (1971)
and Hultman (1967).
Hepatic glucose production
(mmol.min–1)
5
300
200
100
0
Rest
Exercise
Fig. 6.3 Hepatic glycogen concentration in men at rest
following an overnight fast (n = 33) and following an
overnight fast and 60 min of exercise at approximately
75% of maximal oxygen consumption in a second
group of subjects (n = 14). Biopsy samples were
obtained at the same time of day in both groups of
subjects. From Hultman and Nilsson (1971).
insulin concentration and increases in adrenaline
and glucagon with increasing exercise duration
together with afferent nervous feedback from
contracting muscle will stimulate liver glucose
release (for more complete information, see Kjaer
1995).
92
nutrition and exercise
Muscle fibre type responses
The conclusions presented so far have been
based on metabolite changes measured in biopsy
samples obtained from the quadriceps femoris
muscle group. However, it is known that human
skeletal muscle is composed of at least two functionally and metabolically different fibre types.
Type I fibres are characterized as being slow contracting, fatigue resistant, having a low peak
power output and favouring aerobic metabolism
for ATP resynthesis during contraction. Conversely, in comparison, type II fibres are fast contracting, fatigue rapidly, have a high peak power
output and favour mainly anaerobic metabolism
for ATP resynthesis (Burke & Edgerton 1975).
Maximal exercise
Evidence from animal studies performed on
muscles composed of predominantly type I or
type II fibres and from one study performed
using bundles of similar human muscle fibre
types, suggest that the rapid and marked rise and
subsequent decline in maximal power output
observed during intense muscle contraction in
man may be closely related to activation and
rapid fatigue of type II fibres during contraction
(Faulkner et al. 1986).
Figure 6.4 demonstrates glycogen degradation
in type I and type II muscle fibres during
maximal exercise under four different experimental conditions. Notice that during intense
contraction the rates of glycogenolysis are higher
in type II than in type I fibres. This is true for both
dynamic exercise (Greenhaff et al. 1994; treadmill
sprinting) and electrically induced isometric
contractions (Greenhaff et al. 1991, 1993). The
rates of glycogenolysis observed in both fibre
types during treadmill sprinting and intermittent isometric contraction with circulation
.
occluded, are in good agreement with the Vmax. of
phosphorylase measured in both fibre types
(Harris et al. 1976), suggesting that glycogenoly-
Glycogenolytic rate (glucose units, mmol.s–1.kg–1)
5
4
3
2
1
0
Open
circ.
Open circ.
and
adrenaline
Electrical stimulation
Occluded
circ.
Sprinting
Fig. 6.4 Glycogenolytic rates in
type I ( ) and type II (䊐) human
muscle fibres during 30 s of
intermittent electrically evoked
maximal isometric contraction
with intact circulation (circ.), intact
circulation with adrenaline
infusion, occluded circulation and
during 30 s of maximal sprint
running. Adapted from Greenhaff
et al. (1991, 1993, 1994).
carbohydrate metabolism in exercise
sis is occurring at a near maximal rate during
intense exercise. Surprisingly, during intermittent isometric contraction with circulation intact,
when the rest interval between contractions is of
the order of 1.6 s, the rate of glycogenolysis in
type I fibres is almost negligible. The corresponding rate in type II fibres is almost maximal and
similar to that seen during contraction with circulatory occlusion. This suggests that during
maximal exercise glycogenolysis in type II fibres
is invariably occurring at a maximal rate, irrespective of the experimental conditions, while
the rate in type I fibres is probably very much
related to cellular oxygen availability.
Submaximal exercise
In contrast to maximal exercise, the rate of
glycogenolysis during submaximal exercise is
greatest in type I fibres, especially during the
initial period of exercise (Ball-Burnett et al. 1990).
This phenomenon is likely to be the result of differences in the recruitment pattern between
muscle fibre types. If exercise is continued, glycogen utilization occurs in both fibre types but
depletion is observed first in the type I muscle
fibres. The consumption of carbohydrate during
exhaustive submaximal exercise has been shown
to offset the depletion of glycogen specifically in
type I fibres (Tsintzas et al. 1996).
Fatigue mechanisms related to
carbohydrate metabolism
What is clear from the literature is that glycogen
availability per se is not usually considered
to be responsible for fatigue development
during maximal exercise, providing the preexercise glycogen store is not depleted to below
100 mmol · kg -1 dm. It is even unlikely that glycogen availability will limit performance during repeated bouts of exercise, due to the decline
in glycogenolysis and lactate production that
occurs under these conditions. It is more probable that fatigue development during maximal
exercise will be caused by a gradual decline
in anaerobic ATP production caused by the
93
depletion of PCr and a fall in the rate of
glycogenolysis.
Lactic acid accumulation during highintensity exercise is considered to produce
muscle fatigue as a result of H+ and Pi accumulation. An increase in hydrogen ion concentration
will negatively affect phosphorylase activity,
thereby delaying the rate of glycogenolysis, by
delaying transformation of the b form to the a
form (Danforth 1965; Chasiotis 1983) and by
decreasing the HPO42+, the dibasic form of Pi,
which is the substrate for phosphorylase. The
inhibition of PFK discussed previously seems to
be at least partly offset by an increase in the activators of PFK, especially ADP, AMP and Pi, when
the rate of ATP utilization is higher than the rate
of oxidative ATP resynthesis. The increase in
ADP and Pi, especially the H2PO4– form, in acidotic muscle is known to have inhibitory effects
on contractile function (Cook & Pate 1985; Nosek
et al. 1987). However, there is no evidence of a
direct relationship between the decline in muscle
force during contraction and H+ accumulation.
For example, studies involving human volunteers have demonstrated that muscle-force generation following fatiguing exercise can recover
rapidly, despite having a very low muscle pH
value (Sahlin & Ren 1989). The general consensus
at the moment appears to be that the initial generation of muscle force production is dependent
on the capacity to generate ATP but the maintenance of force generation is also pH dependent.
Despite the wealth of information showing
that carbohydrate availability is essential to performance during submaximal exercise, the biochemical mechanism(s) by which fatigue is
brought about in the carbohydrate depleted state
are still unclear. Recent evidence suggests that
carbohydrate depletion will result in an inability
to rephosphorylate ADP to ATP at the required
rate, possibly because of a decrease in the rate of
flux through the TCA cycle as a result of a decline
in muscle TCA cycle intermediates (Sahlin et al.
1990). The consequent rise in ADP concentration
will bring about fatigue, perhaps as a direct
inhibitory effect of ADP and/or Pi on contraction
coupling.
94
nutrition and exercise
Conclusion
The carbohydrate stores of the body, liver and
muscle glycogen, are utilized immediately at
start of exercise. Glucose output from the liver
closely matches the increased glucose requirement of the contracting muscles, keeping the
blood glucose concentration unchanged during
submaximal exercise. Blood glucose levels are
normally seen only to increase in the initial
period of intense exercise and to fall when the
hepatic glycogen store is depleted near to
exhaustion. The regulation of the hepatic glucose
release is a complex process dependent on both
hormonal control and feedback signals from contracting muscles.
Glucose uptake by exercising muscle is
directly related to exercise intensity and regulated by muscle blood flow and facilitated by
increased glucose transport capacity of the
plasma membrane of the contracting muscle. The
maximal rate of glucose uptake at a normal blood
glucose concentration is about 0.4 mmol · min–1 ·
kg–1 exercising muscle. Glucose utilization is also
dependent on the glucose phosphorylation
capacity mediated by the activity of hexokinase.
The major carbohydrate store of the body is
muscle glycogen, which is used in concert with
the hepatic glycogen store to provide the exercising muscle with energy.
The rate of utilization is low at rest and during
low-intensity exercise, when blood-borne glucose and free fatty acids are the major sources of
fuel for ATP resynthesis. With increasing exercise
intensity, the use of carbohydrate as an energy
substrate increases gradually to cover almost all
the energy demand of contraction at exercise
intensities near the subject’s maximal oxygen
uptake. The maximal rate of oxidative energy
production from muscle glycogen is of the order
of 35 mmol ATP · min–1 · kg–1 exercising muscle,
corresponding to a glycogen degradation rate of
1 mmol · min–1 · kg–1 wet muscle. The mechanism(s) controlling the integration of fat and carbohydrate utilization during exercise are poorly
understood and, as yet, unresolved.
The muscle glycogen store can also produce
ATP anaerobically and at a rate that is twice that
of oxidative ATP regeneration. Anaerobic energy
delivery can be activated within milliseconds,
while the aerobic energy production needs
several minutes to reach a steady state. Thus,
anaerobic carbohydrate utilization will be important as an energy provider during the transition period between rest and exercise and during
periods of intense exercise when the energy
demand of contraction exceeds the capacity of
oxidative ATP regeneration.
It can be concluded that carbohydrate is used
as fuel at onset of exercise at all intensities and is
an obligatory fuel for the continuation of exercise
at intensities above 50–60% of the subject’s
maximal oxygen uptake. Depletion of the muscle
carbohydrate stores will impair exercise performance at this range of exercise intensities.
Exhaustion of the liver glycogen store during
prolonged exercise results in hypoglycaemia
which also impairs continued exercise
performance.
Carbohydrate metabolism in exercising
muscle is initiated by Ca2+ release from the sarcoplasmic reticulum and thereafter is regulated
by the rate of ATP degradation via the phosphorylation state of the high-energy phosphate pool
(ATP, ADP, AMP, PCr) and Pi. AMP and Pi
concentrations regulate the flux through the
glycolytic pathway while Ca2+ and pyruvate concentrations are the main regulators of PDH activity which, together with the intramitochondrial
concentration of ADP, determines the rate of carbohydrate oxidation. The result is a tight matching of ATP generation from carbohydrate sources
with the ATP demand of contracting muscle.
Other influences on carbohydrate metabolism
during exercise include diet, training status and
hormonal balance.
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