anaplerotic reactions are not as effective as the
alanine aminotransferase reaction and only
allow muscular work at 40–50% of Wmax..
It is far from clear whether dynamic whole-
body exercise as practised by athletes during
competition (cycling or running) leads to net
protein breakdown in muscle and helps to
provide carbon skeletons for synthesis of TCA-
cycle intermediates. Different stable isotope
tracers used to measure protein synthesis and
degradation in laboratory conditions give differ-
ent answers (for reviews, see Chapter 10 and
Rennie 1996). Whole-body measurements with
l-[1-^13 C] leucine suggest that there is net pro-
tein breakdown during exercise, but is not clear
whether this occurs in muscle or in the gut. Fur-
thermore, carbohydrate ingestion during exer-
cise as practised by endurance athletes during
competition reduces net protein breakdown and
amino acid oxidation.
Conclusion
Six amino acids are metabolized in resting
muscle: leucine, isoleucine, valine, asparagine,
aspartate and glutamate. These amino acids
provide the aminogroups and probably the
ammonia required for synthesis of glutamine
and alanine, which are released in excessive
amounts in the postabsorptive state and during
ingestion of a protein-containing meal. Only
leucine and part of the isoleucine molecule can
be oxidized in muscle as they are converted to
acetyl-CoA. The other carbon skeletons are used
solely for de novosynthesis of TCA-cycle interme-
diates and glutamine. The carbon atoms of the
released alanine originate primarily from glycol-
ysis of blood glucose and of muscle glycogen
(about half each in resting conditions). After con-
sumption of a protein-containing meal, BCAA
and glutamate are taken up by muscle and their
carbon skeletons are used for de novosynthesis of
glutamine. About half of the glutamine release
from muscle originates from glutamate taken up
from the blood both after overnight starvation,
prolonged starvation and after consumption of a
mixed meal. Glutamine produced by muscle is
an important fuel and regulator of DNA and
RNA synthesis in mucosal cells and immune
system cells and fulfils several other important
functions in human metabolism.
The alanine aminotransferase reaction func-
tions to establish and maintain high concen-
trations of TCA-cycle intermediates in muscle
during the first 10 min of exercise. The increase in
concentration of TCA-cycle intermediates prob-
ably is needed to increase the rate of the TCA-
cycle and meet the increased energy demand of
exercise. A gradual increase in leucine oxidation
subsequently leads to a carbon drain on the TCA
cycle in glycogen-depleted muscles and may
thus reduce the maximal flux in the TCA cycle
and lead to fatigue. Deamination of amino acids
and glutamine synthesis present alternative
anaplerotic mechanisms in glycogen-depleted
muscles but only allow exercise at 40–50% of
Wmax.. One-leg exercise leads to net breakdown
of muscle protein. The liberated amino acids are
used for synthesis of TCA-cycle intermediates
and glutamine. Today it is not clear whether and
how important this process is in endurance exer-
cise in the field (running or cycling) in athletes
who ingest carbohydrates. It is proposed that the
maximal flux in the TCA cycle is reduced in
glycogen-depleted muscles due to insufficient
TCA-cycle anaplerosis and that this presents a
limitation for the maximal rate of fatty acid oxi-
dation. Interactions between the amino acid pool
and the TCA cycle are suggested to play a central
role in the energy metabolism of the exercising
muscle.References
Ahlborg, G., Felig, P., Hagenfeldt, L., Hendler, R. &
Wahren, J. (1974) Substrate turnover during pro-
longed exercise in man: splanchnic and leg metabo-
lism of glucose, free fatty acids, and amino acids.
Journal of Clinical Investigation 53 , 1080–1090.
Aoki, T.T., Brennan, M.F., Fitzpatrick, G.F. & Knight,
D.C. (1981) Leucine meal increases glutamine and
total nitrogen release from forearm muscle. Journal of
Clinical Investigation 68 , 1522–1528.
Ardawi, M.S.M. & Newsholme, E.A. (1983) Glutamine
metabolism in lymphocytes of the rat. Biochemical
Journal 212 , 835–842.