chemical energy in the form of ATP; in fact,
energy from the hydrolysis of ATP is harnessed
to power all forms of biological work. In muscle,
energy from the hydrolysis of ATP by myosin
ATPase activates specific sites on the contractile
elements, as described previously, causing the
muscle fibre to shorten. The hydrolysis of ATP
yields approximately 31 kJ of free energy per
mole of ATP degraded to ADP and inorganic
phosphate (Pi):
ATP+H 2 OfiADP+H++Pi–31kJ·mol–1ATP
Active reuptake of calcium ions by the sarcoplas-
mic reticulum also requires ATP, as does the
restoration of the sarcolemmal membrane poten-
tial via the action of the Na+–K+-ATPase. There
are three different mechanisms involved in the
resynthesis of ATP for muscle force generation:
1 Phosphocreatine (PCr) hydrolysis.
2 Glycolysis, which involves metabolism of
glucose-6-phosphate (G6P), derived from muscle
glycogen or blood-borne glucose, and produces
ATP by substrate-level phosphorylation
reactions.
3 The products of carbohydrate, fat, protein and
alcohol metabolism can enter the tricarboxylic
acid (TCA) cycle in the mitochondria and be oxi-
dized to carbon dioxide and water. This process
is known as oxidative phosphorylation and
yields energy for the synthesis of ATP.
The purpose of these mechanisms is to regen-
erate ATP at sufficient rates to prevent a signifi-
cant fall in the intramuscular ATP concentration.
The resting concentration of ATP in skeletal
muscle is quite low at about 20–25 mmol · kg–1
dry matter (dm) of muscle, which in itself could
only provide enough energy to sustain a few
seconds of intense exercise. PCr breakdown and
glycolysis are anaerobic mechanisms (that is,
they do not use oxygen) and occur in the sar-
coplasm. Both use only one specific substrate for
energy production (i.e. PCr and G6P). The
aerobic (oxygen-requiring) processes in the mito-
chondria can utilize a variety of different sub-
strates. The sarcoplasm contains a variety of
enzymes which can convert carbohydrates, fats
and proteins into usable substrate, primarily a
2-carbon acetyl group linked to coenzyme A
(acetyl-CoA) which can be completely oxidized
in the mitochondria with the resultant produc-
tion of ATP. A general summary of the main
energy sources and pathways of energy metabo-
lism is presented in Fig. 2.2.Anaerobic metabolism
Phosphocreatine
Some of the energy for ATP resynthesis is sup-
plied rapidly and without the need for oxygen by
PCr. Within the muscle fibre, the concentration of
PCr is about 3–4 times greater than that of ATP.
When PCr is broken down to creatine and inor-
ganic phosphate by the action of the enzyme cre-
atine kinase, a large amount of free energy is
released (43 kJ · mol–1PCr) and, because PCr has a
higher free energy of hydrolysis than ATP, its
phosphate is donated directly to the ADP mole-
cule to reform ATP. The PCr can be regarded as a
back-up energy store: when the ATP content
begins to fall during exercise, the PCr is broken
down, releasing energy for restoration of ATP.
During very intense exercise the PCr store can be
almost completely depleted. There is a close rela-
tionship between the intensity of exercise and the
rate at which PCr is broken down. The reactions
of ATP and PCr hydrolysis are reversible, and
when energy is readily available from other
sources (oxidative phosphorylation), creatine
and phosphate can be rejoined to form PCr:
ADP+PCr+H+¤ATP+Cr – 43 kJ · mol–1PCr
Note that the resynthesis of ATP via breakdown
of PCr buffers some of the hydrogen ions formed
as a result of ATP hydrolysis. The PCr in muscle
is immediately available at the onset of exercise
and can be used to resynthesize ATP at a very
high rate. This high rate of energy transfer corre-
sponds to the ability to produce a high power
output. The major disadvantage of this system is
its limited capacity (Table 2.2); the total amount
of energy available is small. If no other energy
source is available to the muscle, fatigue will
occur rapidly. An additional pathway to regener-
ate ATP when ATP and PCr stores are depleted is
through a kinase reaction that utilizes two mole-