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Stereochemically pure samples of enzymically active (3S)-3-hydroxy-3-methylglutaryl-CoA and its enzymically inactive R diastereomer were prepared in good yield with a genetically engineered catalytic fragment of human 3-hydroxy-3-methylglutaryl-CoA reductase. The inhibitory properties of the R stereoisomer were determined in reactions with 3S and 3RS substrate and were shown to be of partially competitive type. Ki values of competitive inhibitors are shown to be approximately equal if determined with either stereochemically pure substrate or the diastereomeric 3RS mixture containing the inhibitory stereoisomer.

biological chemistry hoppe-seyler

3-Hydroxy-3-methylglutaryl-CoA Reductase Mediates the Preparation of its Substrate Diastereomers and is Inhibited by (3 R )-3-Hydroxy-3-methylgIutaryI-CoA