Kinetic evidence of a distinct regulatory site on 15-hydroxyprostaglandin dehydrogenase.
15-Hydroxyprostaglandin dehydrogenase was inhibited by xylocaine, furosemide, and ethacrynic acid, but was activated by imipramine and other related drugs. Inhibition by xylocaine was uncompetitive with respect to both NAD+ and PGE1. Activation by imipramine was also uncompetitive with respect to both substrates. Kinetic studies on mixed inhibitor and activator showed a competitive pattern of inhibition of xylocaine vs imipramine activation. These studies suggest that either inhibitors or activators interact with the enzyme at a site distinct from substrate and coenzyme binding sites, and that inhibitors and activators probably interact with the enzyme at the same regulatory site.
D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000494:Allosteric Regulation; D000495:Allosteric Site; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D004976:Ethacrynic Acid / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D006911:Hydroxyprostaglandin Dehydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007099:Imipramine / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008012:Lidocaine / Q000494:pharmacology; D009243:NAD / Q000378:metabolism; D011458:Prostaglandins E / Q000378:metabolism; D013552:Swine
D011458:Prostaglandins E; D009243:NAD; D005665:Furosemide; D008012:Lidocaine; D000429:Alcohol Oxidoreductases; D006911:Hydroxyprostaglandin Dehydrogenases; D004976:Ethacrynic Acid; D007099:Imipramine