Reduced amino acid availability inhibits muscle protein synthesis and decreases activity of initiation factor eIF2B

Hisamine Kobayashi, Elisabet Børsheim, Tracy G. Anthony, Daniel L. Traber, John Badalamenti, Scot R. Kimball, Leonard S. Jefferson, Robert R. Wolfe

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

We have examined the effect of a hemodialysis-induced 40% reduction in plasma amino acid concentrations on rates of muscle protein synthesis and breakdown in normal swine. Muscle protein kinetics were measured by tracer methodology using [2H5]phenylalanine and [1-13C]leucine and analysis of femoral arterial and venous samples and tissue biopsies. Net amino acid release by muscle was accelerated during dialysis. Phenylalanine utilization for muscle protein synthesis was reduced from the basal value of 45 ± 8 to 25 ± 6 nmol·min-1·100 ml leg-1 between 30 and 60 min after start of dialysis and was stimulated when amino acids were replaced while dialysis continued. Muscle protein breakdown was unchanged. The signal for changes in synthesis appeared to be changes in plasma amino acid concentrations, as intramuscular concentrations remained constant throughout. The changes in muscle protein synthesis were accompanied by a reduction or stimulation, respectively, in the guanine nucleotide exchange activity of eukaryotic initiation factor (eIF)2B following hypoaminoacidemia vs. amino acid replacement. We conclude that a reduction in plasma amino acid concentrations below the normal basal value signals an inhibition of muscle protein synthesis and that corresponding changes in eIF2B activity suggest a possible role in mediating the response.

Original languageEnglish (US)
Pages (from-to)E488-E498
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume284
Issue number3 47-3
DOIs
StatePublished - Mar 1 2003

Keywords

  • Eukaryotic initiation factor 2B
  • Hemodialysis
  • Stable isotopes
  • Swine

ASJC Scopus subject areas

  • General Medicine

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