TY - JOUR
T1 - Functional heterogeneity of leucine pools in human skeletal muscle
AU - Ljungqvist, Olle H.
AU - Persson, Mai
AU - Charles Ford, G.
AU - Sreekumaran Nair, K.
PY - 1997
Y1 - 1997
N2 - -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 α-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 nig 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 (-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 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.
AB - -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 α-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 nig 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 (-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 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.
KW - Ketoisocaproate
KW - Leucyl-transfer ribonucleic acid
KW - Muscle protein synthesis
UR - http://www.scopus.com/inward/record.url?scp=33745385220&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33745385220&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:33745385220
SN - 0002-9513
VL - 273
SP - E521-E527
JO - American Journal of Physiology
JF - American Journal of Physiology
IS - 3 PART 1
ER -