We propose a new six-compartment model of intracellular muscle kinetics of
leucine and of its transamination product alpha-ketoisocaproic acid (KIC) by
combining systemic tracer infusions of [14C]- and [15N]leucine with the
arterial-deep venous catheterization of the human forearm. Venous [14C]KIC
specific activity (SA) is taken as representative of intracellular [14C]leucine
SA, whereas net [15N]leucine disposal is used to calculate leucine inflow and
outflow across forearm cell membrane(s). In post-absorptive normal subjects,
model-derived rates of intracellular leucine release from and incorporation into
protein were approximately 32% (P = 0.03) and approximately 37% greater (P =
0.025), respectively, than those calculated using a conventional arteriovenous
approach. Forearm fasting proteolysis exceeded protein synthesis (P < 0.025),
whereas leucine oxidation was greater than zero (P < 0.01), suggesting a net
negative leucine (i.e., protein) balance. Leucine inflow from blood to cell
represented approximately 30% of arterial leucine delivery; therefore
approximately 70% of arterial leucine bypassed intracellular metabolism. This
model provides a comprehensive description of regional leucine and KIC kinetics
and new estimates of protein degradation and synthesis across the human forearm.
