Prevention of Cyclic and Triton-induced Increases in Hydroxymethylglutaryl Coenzyme A Reductase and Sterol Synthesis by Puromycin

Injection of Triton WR 1339 into strain A/HeJ mice caused a marked increase in the rate of sterol synthesis from acetate in liver slices and an increase of similar magnitude in the P-hydroxy-@-methylglutaryl (HMG)-coenzyme A reductase activity of liver microsomes.The increases in sterol synthesis and HMG-CoA reductase activity were prevented by puromycin and were variably inhibited by actinomycin D. The mice showed a cycle in the rate of sterol synthesis and HMG-CoA reductase activity during the period from 8 a.m. to 8 p.m. that was inversely correlated with changes in the rate of fatty acid biosynthesis.Treatment with puromycin prevented the cyclic increases in sterol biosynthesis and HMG-CoA reductase activity.The procedure used to determine HMG-CoA reductase utilized gas chromatography to measure 14C-mevalonic acid produced from 314C-HMG-CoA.Some of the properties of the enzyme system are described.