Mechanisms of Inhibition by Mevinolin (MK 803) of Microsome- Bound Radish and of Partially Purified Yeast HMG-CoA Reductase (E C .l.1.1.34)

Abstract

In kinetic studies, mevinolin was a highly specific inhibitor of partially purified yeast HMG-CoA [3-hydroxyl-3-methylglutaryl CoA] reductase (Ki = 3.5 nM towards HMG-CoA) and of microsomal HMG-CoA reductase from etiolated radish seedlings (Ki = 2.2 nM). At low concentrations of NADPH, the inhibitor counteracts the sigmoidal response of plant HMG-CoA reductase activity towards the cosubstrate. At higher concentrations of NADPH, the inhibition pattern is noncompetitive type. These results were compared with those obtained by the use of animal tissue and yeast as an enzyme source in order to discuss model systems probably valid to evaluate properties and regulation of plant as well as yeast HMG-CoA reductase.