Gentisuric acid: metabolic formation in animals and identification as a metabolite of aspirin in man.
Gentisuric acid was synthesized from gentisic acid and glycine ethyl ester. NMR, mass spectrometric and elemental analysis confirmed the product as GU, and physicochemical characteristics were determined. A TLC-densitometric technique was developed to estimate GU and other metabolites of aspirin. Conjugation of gentisic acid with glycine to form GU was catalyzed by a mitochondrial fraction of rat and beef liver. GU was also formed by the rat liver microsomal hydroxylation of salicyluric acid, and phenobarbital pretreatment increased this formation. A random survey showed GU in 76% of SA-positive urines from aspirin-treated patients. Identity of GU in urine from two aspirin-treated patients was confirmed by TLC and mass spectrometric analysis, and hydrolysis of the compound from one patient yielded glycine and gentisic acid. Urine from controls or post-aspirin treatment patients did not show GU by TLC analysis. These results demonstrate for the first time the metabolic formation of GU in animals and its occurrence as a metabolite of aspirin in man.
D000217:Acyltransferases / Q000378:metabolism; D000328:Adult; D000818:Animals; D001241:Aspirin / Q000378:metabolism*; D002417:Cattle; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D005841:Gentisates / Q000138:chemical synthesis / Q000378:metabolism*; D005998:Glycine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism; D000882:Haplorhini; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D006899:Mixed Function Oxygenases / Q000378:metabolism; D011817:Rabbits; D051381:Rats
D005841:Gentisates; D006899:Mixed Function Oxygenases; D000217:Acyltransferases; D001241:Aspirin; D005998:Glycine