Functional heterogeneity of leucine pools in human skeletal muscle.
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.
Ljungqvist
O H
OH
Department of Medicine, University of Vermont, Burlington 05405, USA.
Persson
M
M
Ford
G C
GC
Nair
K S
KS
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002208:Caproates / Q000378:metabolism; D002247:Carbon Isotopes; D004040:Dietary Carbohydrates; D004435:Eating; D002149:Energy Intake; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D000078790:Insulin Secretion; D007651:Keto Acids / Q000097:blood / Q000378:metabolism; D007930:Leucine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D012356:RNA, Transfer, Leu / Q000097:blood / Q000378:metabolism*; D013997:Time Factors
D001786:Blood Glucose; D002208:Caproates; D002247:Carbon Isotopes; D004040:Dietary Carbohydrates; D007328:Insulin; D007651:Keto Acids; D012356:RNA, Transfer, Leu; C013082:alpha-ketoisocaproic acid; D007930:Leucine