Inhibition of prostaglandin endoperoxide synthetase by thiol analogues of prostaglandin.
A variety of thiol compounds inhibited the enzymatic bis-oxygenation of 8,11,14-eicosatrienoic acid to prostaglandin G1, as examined with a purified preparation of prostaglandin endoperoxide synthetase (prostaglandin synthase; 8,11,14-eicosatrienoate, hydrogen-donor:oxygen oxidoreductase; EC 1.14.99.1) from bovine vesicular gland. The hydroperoxide cleavage of prostaglandin G1 producing prostaglandin H1 was not affected by these thiol compounds. Several prostaglandin analogues with a thiol group (9,11-dihydroxy-15S- or 15R-mercaptoprosta-5,13-dienoic acid, 1-mercapto-9,11,15-trihydroxyprosta-5,13-diene, and 1-mercapto-9-oxo-11,15-dihydroxyprosta-5,13-diene) were most potent inhibitors, showing almost complete inhibition at concentrations on the order of 1 muM. Other thiol compounds, such as 2,3-dimercaptopropanol, dithiotherreitol, and dihydrolipoic acid, were also inhibitory but were much less effective. The inhibition, as examined with 9,11-dihydroxy-15S-mercaptoprosta-5,13-dienoic acid and 2,3-dimercaptopropanol, was noncompetitive.
D015126:8,11,14-Eicosatrienoic Acid / Q000378:metabolism; D000818:Animals; D002417:Cattle; D016861:Cyclooxygenase Inhibitors; D008297:Male; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D011453:Prostaglandins / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D013438:Sulfhydryl Compounds; D006899:Mixed Function Oxygenases; D015126:8,11,14-Eicosatrienoic Acid