Besides Blockage of the Synthesis of HMG-CoA Reductase, Cycloheximide also Inhibits its Degradation

Conference paper

Abstract

A major rate-limiting step in the biosynthesis of cholesterol is the conversion of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) to mevalonate (1, 2). The reaction is catalyzed by HMG-CoA reductase, an enzyme with a relatively short half-life. Incubation of mammalian cultured cells with several oxysterols, e.g., 25-hydroxycholesterol, inhibits the activity of HMG-CoA reductase, apparently by suppression of the synthesis of the enzyme (2, 3). In the presence of 25-hydroxycholesterol (2.5 uM) the reductase activity declines to less than a few percent of the controls within a few hours (4). Studies involving determination of HMG-CoA reductase activity after enucleation have suggested the existence of a rapidly turning-over system which are normally responsible for the inactivation and/or degradation of HMG-CoA reductase (5). In an attempt to further study this degradative system I have analyzed the effects of cycloheximide and 25-hydroxycholesterol, alone or in combination on the activity of the reductase.

Keywords

Cholesterol Leucine Cycloheximide Mevalonate Puromycin 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1983

Authors and Affiliations

  • W. Chen

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