Functional heterogeneity of leucine pools in human skeletal muscle

Olle H. Ljungqvist, Mai Persson, G. Charles Ford, K Sreekumaran Nair

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

-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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology
Volume273
Issue number3 PART 1
StatePublished - 1997

Fingerprint

Leucine
Transfer RNA
Skeletal Muscle
Muscle Proteins
Meals
leucylleucine
Acylation
Water
Muscle Cells
Drinking
Healthy Volunteers
Carbohydrates
Amino Acids
Muscles

Keywords

  • Ketoisocaproate
  • Leucyl-transfer ribonucleic acid
  • Muscle protein synthesis

ASJC Scopus subject areas

  • Physiology (medical)

Cite this

Ljungqvist, O. H., Persson, M., Charles Ford, G., & Nair, K. S. (1997). Functional heterogeneity of leucine pools in human skeletal muscle. American Journal of Physiology, 273(3 PART 1).

Functional heterogeneity of leucine pools in human skeletal muscle. / Ljungqvist, Olle H.; Persson, Mai; Charles Ford, G.; Nair, K Sreekumaran.

In: American Journal of Physiology, Vol. 273, No. 3 PART 1, 1997.

Research output: Contribution to journalArticle

Ljungqvist, OH, Persson, M, Charles Ford, G & Nair, KS 1997, 'Functional heterogeneity of leucine pools in human skeletal muscle', American Journal of Physiology, vol. 273, no. 3 PART 1.
Ljungqvist, Olle H. ; Persson, Mai ; Charles Ford, G. ; Nair, K Sreekumaran. / Functional heterogeneity of leucine pools in human skeletal muscle. In: American Journal of Physiology. 1997 ; Vol. 273, No. 3 PART 1.
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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.

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