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

From the ¹ From The Jackson Laboratory, Bar Harbor, Maine 04609

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 ß-hydroxy-ß-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.

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