substantially increase the glycolytic rate during
exercise due to the glycogen breakdown defect in
muscle and they therefore do not increase muscle
pyruvate. The arterial alanine concentration does
not increase in these patients during exercise
(Wagenmakers et al. 1990) and the muscle only
produces alanine by means of protein degrada-
tion and not via the alanine aminotransferase
reaction (Wagenmakers et al.1990). This implies
that the anaplerotic capacity of these patients
is substantially reduced compared with that of
healthy subjects. The maximal work rate and
oxygen consumption of these patients during
cycling exercise is between 40% and 50% of the
maximum predicted for their age and build. In
ultra-endurance exercise without carbohydrate
ingestion, healthy subjects have to reduce the
work rate to about the same level when the
glycogen stores have been emptied, suggesting
that muscle glycogen indeed is needed to main-
tain high work rates, potentially by means of its
ability to establish and maintain high concentra-
tions of TCA-cycle intermediates.
Alternative anaplerotic reactions in
glycogen-depleted muscles
From the previous sections it has become clear
that the alanine aminotransferase reaction plays
an important role in the establishment and main-
tenance of adequate concentrations of TCA-cycle
intermediates during exercise. In the glycogen-
depleted state, glucose released from the liver by
glycogenolysis and gluconeogenesis and glucose
absorbed from the gut following oral ingestion
of carbohydrates may provide another source of
pyruvate to serve as a driving force for synthesis
of TCA-cycle intermediates via the alanine
aminotransferase reaction. This, in fact, may
explain why higher exercise intensities can be
maintained for prolonged periods when athletes
ingest carbohydrates during exercise. Other
mechanisms that may generate TCA-cycle in-
termediates are increased deamination rates of
amino acids in muscle. Increased deamination
of amino acids indeed has been observed dur-
ing prolonged one-leg exercise by Van Hall et
128 nutrition and exercise
al.(1995b). Deamination of valine, isoleucine,
aspartate, asparagine and glutamate in contrast
to transamination does not use a-ketoglutarate
as amino group acceptor. Deamination therefore
leads to net production of ammonia and net syn-
thesis of TCA-cycle intermediates (see Fig. 9.1).
During prolonged one-leg exercise at 60–65% of
the maximal one-leg-power output, we also
observed an excessive net breakdown rate
of muscle protein (Wagenmakers et al. 1996a).
During one-leg exercise, the workload per kilo-
gram of muscle in the small muscle group used
(maximally 3 kg) is exceedingly high and this
may be the reason why one-leg exercise leads
to net protein degradation (protein synthesis <
protein degradation) in muscle. The amino acid
exchange observed under these conditions indi-
cated that BCAA and glutamate released by the
net breakdown of muscle protein and taken up
from the circulation were used for net synthe-
sis of TCA-cycle intermediates and glutamine.
Removal of amino groups from muscle in the
form of glutamine provides another mechanism
for net synthesis of TCA-cycle intermediates
(Wagenmakers et al. 1996b) as illustrated by the
following net reactions (see Fig. 9.1 for the com-
plete metabolic pathways):
2 glutamate > glutamine+a-ketoglutarate
valine+isoleucine > succinyl-CoA+glutamine
aspartate+isoleucine > oxaloacetate+glutamine
An excessive release of ammonia and glutamine
and excessive net breakdown of muscle protein
(severalfold more than in one-leg exercise in
healthy subjects) also was observed during
two-legged cycling in patients with McArdle’s
disease (Wagenmakers et al. 1990), indicating that
deamination of amino acids and synthesis of
glutamine and TCA-cycle intermediates from
glutamate and BCAA also provided alternative
mechanisms of TCA-cycle anaplerosis in this
muscle disease with zero glycogen availability
and low pyruvate concentrations. The fact that
high exercise intensities cannot be maintained by
these patients and in glycogen-depleted mus-
cles seems to indicate that these alternative