A model of skeletal muscle leucine kinetics measured across the human forearm

• Published in: The American journal of physiology Vol. 269; no. 1 Pt 1; p. E127
• Main Authors: Tessari, P, Inchiostro, S, Zanetti, M, Barazzoni, R
• Format: Journal Article
• Language: English
• Published: United States 01.07.1995
• Subjects: Adult; Forearm; Humans; Leucine - pharmacokinetics; Male; Models, Biological; Muscle, Skeletal - metabolism
• ISSN: 0002-9513; 2163-5773
• DOI: 10.1152/ajpendo.1995.269.1.e127

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.