Abstract
Cycloheximide at concentrations above 18 μM produced a 93% inhibition of total protein synthesis measured by valine incorporation in the perfused rat liver. Rates of protein degradation were estimated by perfusing livers prelabeled in vivo with L-[1- 14C]valine with medium containing 15 mM L-valine. Thus, labeled valine released from liver protein during perfusion was greatly diluted and reincorporation of label was minimized. Cycloheximide at 18 μM inhibited protein degradation by over 60%, after a delay of 15–20 min. Associated with these effects were dose-dependent increases in the rates of glucose and urea production. Glucose production increased 3 fold, from 0.54 ± 0.07 in control to 1.85 ± 0.24 μmol/min/100 g rat in cycloheximide-treated livers. Urea production increased from 0.24 ± 0.02 to 0.62 ± 0.06 μmol/min/100 g rat. No changes in liver glycogen or cyclic AMP content were seen. The data suggest that inhibition of protein synthesis provides an increased availability of intracellular amino acids and that many of these are rapidly degraded, yielding urea and glucose. This is supported by the fact that intracellular alanine levels were significantly increased following cycloheximide treatment. It is possible that the inhibition of protein degradation by cycloheximide is due to altered intracellular pools of amino acids or their metabolites.
Published Version
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