Functional heterogeneity of leucine pools in human skeletal
muscle.
Ljungqvist, Olle H., Mai Persson, G. Charles Ford, K. Sreekumaran Nai.
Endocrine Research Unit, Division of Endocrinology and Metabolism,
Mayo Clinic and Mayo Foundation, Rochester, MN 55905 and Department
of Medicine, University of Vermont, Burlington, VT 05405.
APStracts 4:0108E, 1997.
Current models to measure muscle protein synthesis in humans assume a
homogenous intracellular amino acid pool. This assumption was tested
by measuring the isotopic enrichment of leucine and its
transamination product ([alpha]-ketoisocaproate or KIC) in plasma and
muscle tissue fluid and comparing them with that of leucyl t-RNA
during a continuous infusion of L[1-13C]leucine in 12 healthy
subjects. Six subjects were studied twice while drinking carbohydrate
(0.42kcal/kg) drink /every 20 min for 11h or the same volume of
water. Six others took an isocaloric mixed meal providing 14 mg
protein/kg every 20 minutes and water. Enrichment of plasma and
tissue fluid KIC and plasma leucine were consistently higher than
that of leucyl-tRNA and tissue fluid leucine (P<0.01), whereas the
enrichment of leucyl-tRNA was equivalent to that of tissue fluid
leucine in all experiments. Furthermore, the ratio of enrichment of
leucyl-tRNA to that of plasma leucine and KIC decreased following the
mixed meal, while that of leucyl-tRNA to tissue fluid leucine
remained constant. The enrichment of KIC was closer (17% lower) to
that of plasma leucine than that of leucyl-tRNA (43% higher),
indicating that the transamination pool derived more leucine from
extracellular sources than the acylation pool. We conclude that the
use of plasma KIC enrichment as a surrogate measure of leucyl tRNA
enrichment substantially underestimates of muscle protein synthetic
rates in humans, whereas tissue fluid leucine enrichment is a valid
surrogate measure. In addition, the differences in enrichment of
leucyl tRNA and KIC support a regulated cytoplasmic trafficking of
leucine in muscle cells.
Received 14 February 1997; accepted in final form 23 April 1997.
APS Manuscript Number E73-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 13 May 1997