34 nutrition and exercise
ATP resynthesis. Anaerobic glycolysis involves
several more steps than PCr hydrolysis.
However, compared with oxidative phosphory-
lation, it is still very rapid. It is initiated at the
onset of contraction, but, unlike PCr hydrolysis,
does not reach a maximal rate until after 5 s of
exercise and can be maintained at this level for
several seconds during maximal muscle force
generation (Fig. 2.7). The mechanism(s) responsi-
ble for the eventual decline in glycolysis during
maximal exercise have not been resolved. Exer-
cise at an intensity equivalent to 95–100% V
.
o2max.
can be sustained for durations approaching
5 min before fatigue is evident. Under these con-
ditions, CHO oxidation can make a significant
contribution to ATP production, but its relative
importance is often underestimated.
Fatigue has been defined as the inability to
maintain a given or expected force or power
output and is an inevitable feature of maximal
exercise. Typically, the loss of power output or
force production is likely to be in the region of
40–60% of the maximum observed during 30 s of
all-out exercise. Fatigue is not a simple process
with a single cause; many factors may contribute
to fatigue. However, during maximal short dura-
tion exercise, it will be caused primarily by a
gradual decline in anaerobic ATP production or
increase in ADP accumulation caused by a deple-
tion of PCr and a fall in the rate of glycolysis. In
high-intensity exercise lasting 1–5 min, lactic acid
accumulation may contribute to the fatigue
process. At physiological pH values, lactic acid
almost completely dissociates into its constituent
lactate and hydrogen ions; studies using animal
muscle preparations have demonstrated that
direct inhibition of force production can be
achieved by increasing hydrogen and lactate ion
concentrations. A reduced muscle pH may cause
some inhibition of PFK and phosphorylase,
reducing the rate of ATP resynthesis from glyco-
lysis, though it is thought that this is unlikely to
be important in exercising muscle because the in
vitro inhibition of PFK by a reduced pH is
reversed in the presence of other allosteric activa-
tors such as AMP (Spriet 1991). It would also
appear that lactate and hydrogen ion accumula-
tion can result in muscle fatigue independent of
one another but the latter is the more commonly
cited mechanism. However, although likely to be
related to the fatigue process it is unlikely that
both lactate and hydrogen ion accumulation is
wholly responsible for the development of
muscle fatigue. For example, studies involving
human volunteers have demonstrated that
muscle force generation following fatiguing
exercise can recover rapidly, despite also having
a very low muscle pH value. The general consen-
sus at the moment appears to be that the mainte-
nance of force production during high-intensity
exercise is pH dependent, but the initial force
generation is more related to PCr availability.
One of the consequences of rapid PCr hydroly-
sis during high-intensity exercise is the accumu-
lation of Pi, which has been shown to inhibit
muscle contraction coupling directly. However,
the simultaneous depletion of PCr and Piaccu-
mulation makes it difficult to separate the effect
of PCr depletion from Piaccumulationin vivo.
This problem is further confounded by the paral-
lel increases in hydrogen and lactate ions which
occur during high-intensity exercise. All of these
metabolites have been independently implicated
with muscle fatigue.
As described earlier, calcium release by
the sarcoplasmic reticulum as a consequence of
muscle depolarization is essential for the activa-
tion of muscle contraction coupling. It has been
demonstrated that during fatiguing contractions
there is a slowing of calcium transport and pro-
gressively smaller calcium transients which
has been attributed to a reduction in calcium
reuptake by the sarcoplasmic reticulum and/or
increased calcium binding. Strong evidence that
a disruption of calcium handling is responsible
for fatigue comes from studies showing that the
stimulation of sarcoplasmic reticulum calcium
release caused by the administration of calcium
to isolated muscle can improve muscle force pro-
duction, even in the presence of a low muscle pH.
Alternatively, fatigue during high-intensity exer-
cise may be associated with an excitation-
coupling failure and possibly a reduced nervous
drive due to reflex inhibition at the spinal level.