in this process (Backwell et al., 1996;
Bequette and Backwell, 1997).
Amino Acid Flux Across Muscle
The balance of the movement of individual
amino acids across muscle tissue is deter-
mined by a number of competing pathways
of metabolism. Skeletal muscle is the major
protein store within the body, and in
growing animals the rate of accretion is
dependent upon amino acid supply,
hormonal status and the relationship
between synthetic and degradative path-
ways within the tissue-protein turnover.
Small changes in the balance between
these two latter processes can have a signi-
ficant effect on rates of protein deposition
and therefore production efficiency (Harris
et al., 1992; Sève and Ponter, 1997). Amino
acid supply to, and flux from, muscle has
been measured by a number of groups, and
early work by Felig et al. (1973) established
the presence of the glucose–alanine cycle
in which alanine synthesized in muscle
transfers amino groups to the liver and
provides carbon for gluconeogenesis,
thereby recycling glucose while disposing
of the end-products of muscle amino acid
degradation. This pathway, however,
appears to be of minor importance in
ruminant animals when compared with
non-ruminants. The metabolism of the
branched-chain amino acid (BCAA) leucine
by muscle tissue also appears to differ
between the two groups of animal species.
In non-ruminants, skeletal muscle oxidizes
a greater proportion of leucine derived
from muscle protein degradation than in
ruminants, and the transamination product
-ketoisocaproate (KIC) is re-aminated
extensively in the liver. In the fasted
ruminant, however, most of the leucine
derived from muscle turnover is released,
and in both gut and liver KIC and leucine
contribute towards protein synthesis rather
than acting as oxidative substrates (Pell et
al., 1986).
In addition to BCAAs, the role(s) of
glutamine in the integration of nitrogen
metabolism between tissues has also been
an area of active research. It is the most
abundant amino acid in the body, and
muscle tissue appears to act as a source of
supply for the requirements of gut and
immune tissues during periods of meta-
bolic stress. This efflux of glutamine has
been demonstrated in both fed and fasted
ruminants (McCormick and Webb, 1982),
and in rats glutamine output from skeletal
muscle increased as the plasma concentra-
tion decreased (Ardawi and Jamal, 1990).
Given the putative roles of glutamine in
energy metabolism and also in the provi-
sion of amino groups for nucleic acid
synthesis in rapidly dividing cells (e.g.
intestinal enterocytes and lymphocytes), it
is apparent that amino group transfer from
BCAAs in order to sustain glutamine out-
put by muscle (Lobley, 1991) may repre-
sent a further integration of amino acid
metabolism across the tissue.
As with other tissues, the form and
complexity of amino acid supply to the
muscle are still an area of debate. Arterio-
venous studies by McCormick and Webb
(1987) and Danilson et al. (1987) have
suggested that peptides and serum proteins
have the potential to contribute to amino
acid flux to and from the tissue. Their
studies also suggested that the nature of the
diets fed to calves influenced the pattern of
this flux. The hypothesis that hepatic
protein output may provide a source of
amino acids for peripheral tissues has been
investigated (Connell et al., 1997) in a
study which measured changes in liver
albumin synthesis in fed and fasted sheep.
It was concluded that insufficient albumin
was available to account for the shortfall in
post-hepatic provision of free amino acids.
A further evaluation of the potential role of
a range of liver export proteins in the
provision of a balanced supply of amino
acids to meet the requirements for muscle
protein accretion (Lobley and Milano,
1997), however, suggests that they could
make an important contribution to the
supply of histidine and phenylalanine. At
present, the lack of specific methodology to
investigate the fate(s) of plasma proteins
across tissue beds is preventing further
progress in this area.Inter-organ Amino Acid Flux 57