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.
D000214:Acyl Coenzyme A / Q000494:pharmacology*; D000818:Animals; D003065:Coenzyme A / Q000494:pharmacology; D003958:Diamide / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008634:Mersalyl / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D013439:Sulfhydryl Reagents / Q000494:pharmacology*
D000214:Acyl Coenzyme A; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013439:Sulfhydryl Reagents; D003958:Diamide; D008634:Mersalyl; D003065:Coenzyme A