Functional heterogeneity of leucine pools in human skeletal muscle

• Published in: The American journal of physiology Vol. 273; no. 3 Pt 1; p. E564
• Main Authors: Ljungqvist, O H, Persson, M, Ford, G C, Nair, K S
• Format: Journal Article
• Language: English
• Published: United States 01.09.1997
• Subjects: Adult; Blood Glucose - metabolism; Caproates - metabolism; Carbon Isotopes; Dietary Carbohydrates; Eating; Energy Intake; Female; Humans; Infusions, Intravenous; Insulin - blood; Insulin - metabolism; Insulin Secretion; Keto Acids - blood; Keto Acids - metabolism; Leucine - administration & dosage; Leucine - blood; Leucine - metabolism; Male; Muscle, Skeletal - metabolism; RNA, Transfer, Leu - blood; RNA, Transfer, Leu - metabolism; Time Factors
• ISSN: 0002-9513; 2163-5773
• DOI: 10.1152/ajpendo.1997.273.3.e564

Current models to measure muscle protein synthesis in humans assume a homogeneous intracellular amino acid pool. This assumption was tested by measuring the isotopic enrichment of leucine and its transamination product alpha-ketoisocaproate (KIC) in plasma and muscle tissue fluid and comparing them with that of leucyl-tRNA during a continuous infusion of L-[1-13C]leucine in 12 healthy subjects. Six subjects were studied twice while drinking a carbohydrate (0.42 kcal/kg) drink every 20 min for 11 h or the same volume of water. Six others took an isocaloric mixed meal providing 14 mg protein/kg every 20 min and water. Enrichment of plasma and tissue fluid KIC and plasma leucine was 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 after the mixed meal, whereas that of leucyl-tRNA to tissue fluid leucine remained constant. The enrichment of KIC was closer (approximately 17% lower) to that of plasma leucine than that of leucyl-tRNA (approximately 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 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.