extremely variable and suffer from experi-
mental problems in the accurate measure-
ment of hepatic portal venous and arterial
blood flow and corresponding amino acid
concentrations, the venous-arterio concen-
tration differences often being similar to
levels of analytical precision. Absorbed
amino acids have four potential fates in the
liver (Wray-Cahen et al., 1997): (i) retention
in the free form as expanded intra- and
extravascular fluid; (ii) conversion to
specific nitrogenous metabolites (e.g.
aromatic amino acids to neurotransmitters,
glycine to hippurate, synthesis of small
oligopeptides); (iii) oxidation to produce
energy and non-nitrogenous intermediary
metabolites; and (iv) incorporation into
hepatic and export proteins. An additional
fate of amino acids linked to catabolism of
the carbon skeleton is their role as a method
of detoxifying excess ammonia arriving at
the liver (Parker et al., 1995). For example,
removal of amino acids by the liver is
increased with increased portal absorption
of ammonia N (Maltby et al., 1991;
Reynolds et al., 1991). The mechanism for
the increase in liver removal of amino
acids under dietary conditions which
result in increased ammonia production is
unclear; however, it has been suggested
that this may be due to an increased
requirement for amino acid N in trans-
amination reactions to generate glutamate
and aspartate required for urea biosyn-
thesis (Reynolds, 1992). Under normal
conditions, mitochondrial and cytosolic
aspartate–glutamate transamination pools
are in equilibrium (Cooper et al., 1991),
and the reversible action of glutamate
dehydrogenase means that both N atoms in
the urea molecule can arise from either
NH 3 or amino acids (Meijer et al., 1990). In
contrast, under conditions of high urea
flux, the mitochondrial supply of NH 3 may
not be sufficient for both N moieties,
inducing the obligatory use of amino acid
N to maintain urea synthesis. Increased
oxidation of alanine and reduced gluco-
neogenesis from this amino acid have been
observed in vitroin hepatocytes isolated
from sheep fed soluble nitrogen in the form
of urea (Mutsvangwa et al., 1996), and
Lobley et al. (1995) showed that oxidation
of [1–^14 C]leucine was increased during
infusions of NH 4 Cl into the mesenteric
vein. Studies in vitro with isolatedInter-organ Amino Acid Flux 55Table 3.3.Hepatic fractional extractions of absorbed amino acids from the plasma across the liver of sheep,
pigs and cattle (reproduced with permission from Wray-Cahen et al., 1997).
Wolff et al. Rérat et al. Lobley et al. Lobley et al. Wray-Cahen et al.
(1972) (1992)a (1995)b (1996) (1997)c
Amino acid Sheep Pigs Sheep Sheep Cattle
Glycine 2.54 1.16 0.97 1.07 0.73
Alanine 1.39 0.86 0.69 1.14 0.54
Serine 1.13 0.63 0.97 0.75 0.37
Proline 0.91 0.53 0.47 0.96 0.47
Tyrosine 1.42 0.44 0.85 0.83 0.63
Arginine 2.53 0.48 0.73 0.72 0.70
Valine 0.58 0.48 0.43 0.47 0.25
Isoleucine 0.37 0.54 0.28 0.50 0.49
Leucine 0.36 0.50 0.56 0.34 0.30
Methionine 1.00 0.63 1.21 0.53 0.83
Phenylalanine 1.36 0.74 0.84 0.77 0.87
Lysine 0.81 0.50 0.64 0.57 0.31
Histidine 1.50 0.51 1.16 1.09 0.50
Threonine 1.05 0.62 0.44 0.85 0.49
aMean value for peptide and free amino acid intraduodenal infusions.
bValues for blood only and mean of plus and minus exogenous ammonia infusion.
cValues during intramesenteric amino acid infusion corrected for basal level.