it would interfere with cell function. The normal
pH of the muscle cell at rest is about 7.1, but this
can fall to as low as 6.4 in high-intensity exercise,
when large amounts of lactate are formed. At this
pH, the contractile mechanism begins to fail, and
some inhibition of key enzymes, such as phos-
phorylase and phosphofructokinase, may occur.
A low pH also stimulates free nerve endings in
the muscle, resulting in the perception of pain.
Although the negative effects of the acidosis
resulting from lactate accumulation are often
stressed, it must be remembered that the energy
made available by anaerobic glycolysis allows
the performance of high-intensity exercise that
would otherwise not be possible.
Aerobic metabolism
As an alternative to conversion to lactate, pyru-
vate may undergo oxidative metabolism to CO 2
and water. This process occurs within the mito-
chondrion, and pyruvate which is produced in
the sarcoplasm is transported across the mito-
chondrial membrane by a specific carrier protein.
The first step to occur within the mitochondrion
is the conversion, by oxidative decarboxylation,
of the three-carbon pyruvate to a two-carbon
acetate group which is linked by a thio-ester
bond to coenzyme A (CoA) to form acetyl-CoA.
This reaction, in which NAD+is converted to
NADH, is catalysed by the pyruvate dehydro-
genase enzyme complex. Acetyl-CoA is also
formed from the metabolism of fatty acids within
the mitochondria, in a metabolic pathway called
b-oxidation which, as its name implies, is an
oxygen-requiring process.
Acetyl-CoA is oxidized to CO 2 in the TCA
cycle: this series of reactions is also known as
the Krebs cycle, after Hans Krebs, who first
described the reactions involved, or the citric
acid cycle, as citrate is one of the key intermedi-
ates in the process. The reactions involve combi-
nation of acetyl-CoA with oxaloacetate to form
citrate, a six-carbon TCA. A series of reactions
leads to the sequential loss of hydrogen atoms
and CO 2 , resulting in the regeneration of
oxaloacetate:
26 nutrition and exercise
acetyl-CoA+ADP+Pi+3NAD++FAD+3H 2 Ofi
2CO 2 +CoA+ATP+3NADH+3H++FADH 2Since acetyl-CoA is also a product of fatty acid
oxidation, the final steps of oxidative degrada-
tion are therefore common to both fat and carbo-
hydrate. The hydrogen atoms are carried by the
reduced coenzymes NADH and flavin adenine
dinucleotide (FADH 2 ). These act as carriers and
donate pairs of electrons to the electron transport
chain allowing oxidative phosphorylation with
the subsequent regeneration of ATP from ADP.
A summary of the reactions involved in the
TCA cycle is shown in Fig. 2.4. Note that molecu-
lar O 2 does not participate directly in the reac-
tions of the TCA cycle. In essence, the most
important function of the TCA cycle is to gener-
ate hydrogen atoms for their subsequent passage
to the electron transport chain by means of
NADH and FADH 2 (Fig. 2.5). The aerobic process
of electron transport-oxidative phosphorylation
regenerates ATP from ADP, thus conserving
some of the chemical potential energy contained
within the original substrates in the form of high-
energy phosphates. As long as there is an ade-
quate supply of O 2 , and substrate is available,
NAD+and FAD are continuously regenerated
and TCA metabolism proceeds. This system
cannot function without the use of oxygen. For
each molecule of NADH that enters the electron
transport chain, three molecules of ATP are gen-
erated, and for each molecule of FADH 2 , two
molecules of ATP are formed. Thus, for each mol-
ecule of acetyl-CoA undergoing complete oxida-
tion in the TCA cycle, a total of 12 ATP molecules
are formed.
The transfer of electrons through the electron
transport chain located on the inner mitochond-
rial membrane causes hydrogen ions or protons
(H+) from the inner mitochondrial matrix to be
pumped across the inner mitochondrial mem-
brane into the space between the inner and outer
mitochondrial membranes. The high concentra-
tion of positively charged hydrogen ions in this
outer chamber cause the H+ions to flow back into
the mitochondrial matrix through an ATP syn-
thase protein complex embedded in the inner