The Turnover of Microsomal Reduced Nicotinamide Adenine Dinucleotide Phosphate-Cytochrome c Reductase in the Livers of Mice Treated with Phenobarbital

Abstract

Abstract When mice received injections twice daily of sodium phenobarbital there was a 2- to 4-fold increase in microsomal reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase within 4 days. In order to measure the turnover of the enzyme, tritiated l-leucine was injected 24 hours prior to treatment. The half-time for loss in vivo of radioactivity from enzyme protein averaged 2.8 days in controls, but there was no loss of radioactivity from the enzyme in phenobarbital-treated animals. There was little change in specific activity, since decreased breakdown in treated animals was balanced by increased synthesis of unlabeled protein. The 90-min incorporation of l-leucine-3H into microsomal NADPH-cytochrome c reductase was increased 2- to 3-fold in mice pretreated for 2 or more days with sodium phenobarbital. The accumulation of microsomal NADPH-cytochrome c reductase in animals treated with barbiturates seems to result from both a decreased rate of breakdown and an increased rate of synthesis.