the blood glucose can make to carbohydrate
metabolism in the active muscles.
If glycogen, rather than blood glucose, is the
substrate for glycolysis, the first step is to split off
a single glucose molecule. This is achieved by the
enzyme glycogen phosphorylase, and the pro-
ducts are glucose-1-phosphate and a glycogen
molecule that is one glucose residue shorter than
the original. The substrates are glycogen and
inorganic phosphate, so, unlike the hexokinase
reaction, there is no breakdown of ATP in this
first reaction. Phosphorylase acts on the a-1,4
carbon bonds at the free ends of the glycogen
molecule, but cannot break the a-1,6 bonds
forming the branch points. These are hydrolysed
by the combined actions of a debranching
enzyme and amylo-1,6-glucosidase, releasing
free glucose which is quickly phosphorylated to
G6P by the action of hexokinase. There is an
accumulation of free glucose within the muscle
cell only in very high-intensity exercise where
glycogenolysis is proceeding rapidly: because
there are relatively few a-1,6 bonds, no more
than about 10% of the glucose residues appear as
free glucose. The enzyme phosphoglucomutase
ensures that glucose-1-phosphate formed by the
action of phosphorylase on glycogen is rapidly
converted to G6P, which then proceeds down the
glycolytic pathway.
The sequence of reactions that convert G6P to
pyruvate is shown in Fig. 2.3. Briefly, following a
further phosphorylation, the glucose molecule is
cleaved to form two molecules of the three-
carbon sugar glyceraldehyde-3-phosphate. The
second stage of glycolysis involves the conver-
sion of this into pyruvate, accompanied by the
formation of ATP and reduction of nicotinamide
adenine dinucleotide (NAD+) to NADH.
The net effect of glycolysis can thus be seen to
be the conversion of one molecule of glucose to
two molecules of pyruvate, with the net forma-
tion of two molecules of ATP and the conversion
of two molecules of NAD+to NADH. If glycogen
rather than glucose is the starting point, three
molecules of ATP are produced, as there is no
initial investment of ATP when the first phospho-
rylation step occurs. Although this net energy
yield appears to be small, the relatively large car-
24 nutrition and exercise
bohydrate store available and the rapid rate at
which glycolysis can proceed mean that the
energy that can be supplied in this way is crucial
for the performance of intense exercise. The
800-m runner, for example, obtains about 60% of
the total energy requirement from anaerobic
metabolism, and may convert about 100 g of car-
bohydrate (mostly glycogen, and equivalent to
about 550 mmol of glucose) to lactate in less than
2 min. The amount of ATP released in this way
(three ATP molecules per glucose molecule
degraded, about 1667 mmol of ATP in total) far
exceeds that available from PCr hydrolysis. This
high rate of anaerobic metabolism allows not
only a faster ‘steady state’ speed than would be
possible if aerobic metabolism alone had to be
relied upon, but also allows a faster pace in the
early stages before the cardiovascular system has
adjusted to the demands and the delivery and
utilization of oxygen have increased in response
to the exercise stimulus.
The reactions of glycolysis occur in the cyto-
plasm of the cell and some pyruvate will escape
from tissues such as active muscle when the rate
of glycolysis is high, but most is further metabo-
lized. The fate of the pyruvate produced by gly-
colysis during exercise will depend not only on
factors such as exercise intensity, but also on the
metabolic capacity of the tissue. When glycolysis
proceeds rapidly, the problem for the cell is that
the availability of NAD+, which is necessary as
a cofactor in the glyceraldehyde-3-phosphate
dehydrogenase reaction, becomes limiting. The
amount of NAD+in the cell is very small (only
about 0.8 mmol · kg–1dm) relative to the rate at
which glycolysis can proceed. In high-intensity
exercise, the rate of turnover of ATP can be about
8 mmol · kg–1dm·s–1. If the NADH formed by
glycolysis is not reoxidized to NAD+at an equal
rate, glycolysis will be unable to proceed and to
contribute to energy supply.
There are two main processes available for
regeneration of NAD+in muscle. Reduction of
pyruvate to lactate will achieve this, and this
reaction has the advantage that it can proceed in
the absence of oxygen. Lactate can accumulate
within the muscle fibres, reaching much higher
concentrations than those reached by any of the