ratsin vivoby Yoshida et al. (1991), who showed
that leucine C-2 was incorporated into glutamine
after giving l-[1,2-^13 C]leucine. No, or very little,
radioactivity was found in lactate, pyruvate and
alanine during incubation of rat diaphragms
(Wagenmakers et al. 1985) and perfusion of rat
hindquarters (Lee & Davis 1986) with [U-
(^14) C]valine. This implies that there is no active
pathway in muscle for conversion of TCA-cycle
intermediates into pyruvate. It also implies that
the carbon skeleton of the five amino acids that
are converted to TCA-cycle intermediates (Fig.
9.1) cannot be used for complete oxidation
(which is only possible when carbon enters the
TCA-cycle as a 2-carbon acetyl group linked to
coenzyme A (acetyl-CoA) as is the case for
leucine and for part of the isoleucine molecule)
or for pyruvate and alanine synthesis. Therefore,
122 nutrition and exercise
the only fate of these carbon skeletons is synthe-
sis of TCA-cycle intermediates and glutamine
(Fig. 9.1). The question then is what is the source
of the carbon atoms of alanine? The remaining
sources are muscle glycogen and blood glucose
converted by glycolysis into pyruvate (Fig. 9.1).
In agreement with this conclusion Chang and
Goldberg (1978a) reported that over 97% of the
carbons of the alanine, pyruvate and lactate
released by incubated diaphragms were derived
from exogenous glucose.Glucose–alanine cycle revisited
The conclusion of the above section slightly
changes the concept of the glucose–alanine cycle
(Fig. 9.2) (Felig et al. 1970) which by now has
become generally accepted textbook knowledge.MuscleGlucose
GlycogenPyruvateAlanineProtein–NH 2
GlutamineLeu
Ile
Val
Asp
Asn C-skeleton
AmmoniaNon-metabolized
amino acidsBloodGlucoseAlanineGlutamineAmino acidsGlucoseGlucoseGlutamineGlutamineAlanine UreaGlucoseLiverKidneyAmmoniaFuel for gut and immune system
Precursor DNA/RNAFig. 9.2Interorgan relationship in the handling of amino acids. Dashed arrow, prolonged starvation only.