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

83 Citations (Scopus)

Abstract

Current models to measure muscle protein synthesis in humans assume a homogeneous intracellular amine 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 rain for 11 h or the same volume of water. Six ethers took an isocaloric mixed meal providing 14 mg protein/kg every 20 rain 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 - Endocrinology and Metabolism
Volume273
Issue number3 36-3
StatePublished - Sep 1997

Fingerprint

Leucine
Muscle
Transfer RNA
Skeletal Muscle
Tissue
Plasmas
Fluids
Rain
Muscle Proteins
Meals
leucylleucine
Acylation
Ethers
Water
Muscle Cells
Drinking
Amines
Healthy Volunteers
Cells
Carbohydrates

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

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

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 273, No. 3 36-3, 09.1997.

Research output: Contribution to journalArticle

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AB - Current models to measure muscle protein synthesis in humans assume a homogeneous intracellular amine 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 rain for 11 h or the same volume of water. Six ethers took an isocaloric mixed meal providing 14 mg protein/kg every 20 rain 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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