stores become depleted, protein catabolism may
become an increasingly important source of
energy for muscular work.
Regulation of energy metabolism
Intracellular factors
Experiments in which muscle biopsies were
taken before and immediately after exercise indi-
cate that the intramuscular ATP concentration
remains fairly constant. Thus, ATP is constantly
being regenerated by other energy-liberating
reactions, at a rate equal to which it is being used.
This situation provides a sensitive mechanism
for the control of energy metabolism within the
cell. The sum of cellular ATP, ADP and AMP
concentrations is termed the total adenine
nucleotide pool. The extent to which the total
adenine nucleotide pool is phosphorylated is
known as the energy charge of the cell, and it is a
good indicator of the energy status of the cell.
The rate at which ATP is resynthesized during
exercise is known to be regulated by the energy
charge of the muscle cell. For example, the
decline in cellular concentration of ATP at the
onset of muscle force generation and parallel
increases in ADP and AMP concentrations (i.e. a
decline in the energy charge) will directly stimu-
late anaerobic and oxidative ATP resynthesis.
The relatively low concentration of ATP (and
ADP) inside the cell means that any increase in
the rate of hydrolysis of ATP (e.g. at the onset of
exercise) will produce a rapid change in the ratio
of ATP to ADP (and will also increase the intra-
cellular concentration of AMP). These changes,
in turn, activate enzymes which immediately
stimulate the breakdown of intramuscular fuel
stores to provide energy for ATP resynthesis. In
this way, energy metabolism increases rapidly
following the start of exercise.
ATP, ADP and AMP act as allosteric activators
or inhibitors of the enzymatic reactions involved
in PCr, CHO and fat degradation and utilization
(Fig. 2.6). For example, as already mentioned,
creatine kinase, the enzyme responsible for the
rapid rephosphorylation of ATP at the initiation
30 nutrition and exercise
of muscle force generation, is rapidly activated
by an increase in cytoplasmic ADP concentration
and is inhibited by an increase in cellular ATP
concentration. Similarly, glycogen phosphory-
lase, the enzyme which catalyses the conversion
of glycogen to glucose-1-phosphate, is activated
by increases in AMP and Pi(and calcium ion)
concentration and is inhibited by an increase in
ATP concentration.
The rate limiting step in the glycolytic
pathway is the conversion of fructose-6-
phosphate to fructose-1,6-diphosphate and is
catalysed by phosphofructokinase (PFK). The
activity of this complex enzyme is affected by
many intracellular factors, and it plays an impor-
tant role in controlling flux through the pathway.
The PFK reaction is the first opportunity for reg-
ulation at a point which will affect the metabo-
lism of both glucose and glycogen. The activity of
PFK is stimulated by increased concentrations of
ADP, AMP, Pi, ammonia and fructose-6-phos-
phate and is inhibited by ATP, H+, citrate, phos-
phoglycerate and phosphoenolpyruvate. Thus,
the rate of glycolysis will be stimulated when
ATP and glycogen breakdown are increased at
the onset of exercise. Accumulation of citrate and
thus inhibition of PFK may occur when the rate
of the TCA cycle is high and provides a means
whereby the limited stores of CHO can be spared
when the availability of fatty acids is high. Inhi-
bition of PFK will also cause accumulation of
G6P, which will inhibit the activity of hexokinase
and reduce the entry into the muscle of glucose
which is not needed.
Conversion of pyruvate to acetyl-CoA by the
pyruvate dehydrogenase complex is the rate-
limiting step in CHO oxidation and is stimulated
by an increased intracellular concentration of
calcium, and decreased ratios of ATP/ADP,
acetyl-CoA/free CoA and NADH/NAD+ratio
and thus offers another site of regulation of the
relative rates of fat and CHO catabolism. If the
rate of formation of acetyl-CoA from the b-
oxidation of fatty acids is high, as after 1–2 h of
submaximal exercise, then this could reduce the
amount of acetyl-CoA derived from pyruvate,
cause accumulation of phosphoenol pyruvate