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Departments of 1 Surgery, 2 Anesthesiology and 3 Internal Medicine, Metabolism Department, Shriners Burns Hospital, University of Texas Medical Branch, Galveston, Texas 77550; and 4 Department of Cellular and Molecular Physiology, Pennsylvania State College of Medicine, Hershey, Pennsylvania 17033
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 leg1 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.
eukaryotic initiation factor 2B; hemodialysis; stable isotopes; swine
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