Introduction
The body of a 70-kg man contains about 12 kg of
protein (amino acid polymers) and 200–220 g of
free amino acids. There is a continuous exchange
of amino acids between these pools as proteins
are constantly being synthesized and simultane-
ously being degraded (protein turnover). Skele-
tal muscle accounts for some 40–45% of total
body mass and contains some 7 kg of protein, pri-
marily in the form of the contractile (myofibril-
lar) proteins. About 120 g of the free amino acids
are present intracellularly in skeletal muscle,
while only 5 g of free amino acids are present
in the circulation. In the 1840s the German phy-
siologist Von Liebig hypothesized that muscle
protein was the main fuel used to achieve muscu-
lar contraction. After this view had been invali-
dated around 1870 by experimental data, many
exercise physiologists took the opposite stand
and disregarded the amino acid pool in muscle
as playing any role of significance in exercise and
energy metabolism. For over a century the amino
acid pool in skeletal muscle has been considered
as an inert reservoir from which the building
blocks are obtained for the synthesis of contrac-
tile proteins and enzymes. A review is given here
to show that resting skeletal muscle actively par-
ticipates in the handling of amino acids in the
overnight fasted state and following ingestion
of a protein-containing meal and that muscle
actively collaborates with other tissues in these
situations. Major and rapid changes occur in the
muscle free amino acid pool during exercise. Evi-
dence will be presented indicating that changes
in the size of the muscle pool of some amino
acids and in amino acid metabolism play an
important role in the establishment and main-
tenance of a high concentration of tricarboxy-
lic acid (TCA)-cycle intermediates and via this
mechanism in the maintenance of a high aerobic
capacity during prolonged exercise. Amino acids
also seem to play a role in the failure to maintain
high concentrations of TCA-cycle intermediates
during prolonged exercise, an event which
potentially plays a role in the development of
fatigue in glycogen-depleted muscles. The con-
clusion therefore of this chapter will be that
muscle amino acid metabolism occupies a
central place in energy metabolism during exer-
cise not as a direct fuel competing with fatty
acids, blood glucose and glycogen, but as a pre-
cursor for the synthesis of TCA-cyle intermedi-
ates and glutamine.Muscle amino acid metabolism at rest
As an introduction to the changes that occur
during exercise, we will first have a look at the
resting state. In contrast to the liver, which is
able to oxidize most of the 20 amino acids that
are present in proteins, rat and human skele-
tal muscle when incubated in vitrocan oxidize
only six amino acids (Chang & Goldberg 1978a,
1978b; Wagenmakers et al. 1985). These are the
branched-chain amino acids (BCAA—leucine,
isoleucine and valine), glutamate, aspartate and
asparagine (Fig. 9.1).