Selective inhibition of prostaglandin endoperoxide thromboxane isomerase by 1-carboxyalkylimidazoles.
1-Carboxyalkylimidazoles inhibited the conversion of prostaglandin H2 to thromboxane B2 and 12L-hydroxy-5,8,10-heptadecatrienoic acid by a partially purified enzyme (prostaglandin endoperoxide thromboxane isomerase) from bovine platelet microsomes. The degree of the inhibition was dependent on the length of carboxyalkyl chain. 1-Carboxyheptylimidazole was the most potent inhibitor, and an almost complete inhibition was obtained at a concentration on the order of 1 micron. The inhibition, as examined with 1-carboxyheptylimidazole, was of noncompetitive type. These 1-carboxyalkylimidazoles did not affect the formation of prostaglandin H2 from arachidonic acid. Such a selective inhibition was also demonstrated by the reaction of bovine platelet microsomes with arachidonic acid in the presence of 1-carboxyheptylimidazole, resulting in the accumulation of prostaglandin H2 as an intermediate. Furthermore, a series of 1-alkylimidazoles with no carboxyl group also inhibited the isomerase at higher concentrations. However, the inhibition was not specific for the isomerase; namely, the prostaglandin H2 formation from arachidonic acid was also affected.
D000818:Animals; D001095:Arachidonic Acids / Q000097:blood / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism; D002417:Cattle; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006801:Humans; D006880:Hydroxy Acids / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000037:antagonists & inhibitors*; D008861:Microsomes / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D011449:Prostaglandin Endoperoxides; D011463:Prostaglandins H / Q000096:biosynthesis / Q000097:blood; D013929:Thromboxane B2 / Q000097:blood; D013931:Thromboxanes
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D006880:Hydroxy Acids; D007093:Imidazoles; D011449:Prostaglandin Endoperoxides; D011463:Prostaglandins H; D013931:Thromboxanes; D013929:Thromboxane B2; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C022463:prostaglandin endoperoxide thromboxane isomerase