Formation of (4R)- and (4S)-4-hydroxyochratoxin A and 10-hydroxyochratoxin A from Ochratoxin A by rabbit liver microsomes.
Three metabolites were formed from ochratoxin A in the presence of rabbit liver microsomal fractions and NADPH. They were isolated by extraction, thin-layer chromatography, and high-pressure liquid chromatography. Two of them were identified as (4R)- and (4S)-4-hydroxyochratoxin A. It is suggested on the basis of mass and nuclear magnetic resonance spectroscopy that the third metabolite is 10-hydroxyochratoxin A. The formation of the metabolites was inhibited by carbon monoxide and metyrapone and was stimulated when microsomes from phenobarbital-treated animals were used. The results suggest that cytochrome P-450 catalyzes the formation of these metabolites.
D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D009793:Ochratoxins / Q000096:biosynthesis* / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D011817:Rabbits
D009793:Ochratoxins; C025589:ochratoxin A; D009249:NADP; D002248:Carbon Monoxide; C025650:4-hydroxyochratoxin A; C037578:10-hydroxyochratoxin A; D010634:Phenobarbital; D008797:Metyrapone