A MODEL OF SKELETAL-MUSCLE LEUCINE KINETICS MEASURED ACROSS THE HUMAN FOREARM

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 [C-14]- and [N-15]leucine with the arterial-deep venous catheterization of the human forearm. Venous [C-14]KIC specific activity (SA) is taken as representative of intracellular [C-14]leucine SA, whereas net [N-15]leucine disposal is used to calculate leucine inflow and outflow across forearm cell membrane(s). In postabsorptive normal subjects, model-derived rates of intracellular leucine release from and incorporation into protein were approximate to 32% (P = 0.03) and approximate to 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 approximate to 30% of arterial leucine delivery; therefore approximate to 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.