Inhibition of rat liver hydroxymethylglutaryl-CoA reductase by sulfhydryl reagents, coenzyme A esters and synthetic compounds.

The activity of the microsomal 3-hydroxy-3-methylglutaryl-coenzyme A reductase was assayed with a procedure based on the extraction of the product mevalonolactone in a benzene phase. Diamide is an uncompetitive inhibitor of the reaction, while coenzyme A disulfide and tetraethylthiouram disulfide act as non-competitive inhibitors. Diamide inhibition cooperatively increases with the inhibitor concentration. HMG produces a decrease in enzyme activity that combines with that of coenzyme A disulfide. Both CoASH and coenzyme A esters strongly inhibit the reductase activity. Three new synthetic compounds with either thio-ether or thio-ester groups also show inhibitory effect on the enzyme activity.