Comparative in vitro metabolism of aflatoxicol by liver preparations from animals and humans.
The metabolism of [14C]aflatoxicol by liver postmitochondrial and microsomal fractions from humans and eight other species was compared. A major metabolic pathway involves the dehydrogenation of aflatoxicol yielding aflatoxin B1. Human liver preparations were more active in this regard than preparations from any of the other species tested. The aflatoxicol dehydrogenase activity was mainly associated with the microsomal fraction and required a hydrogen acceptor (e.g., nicotinamide adenine dinucleotide phosphate), but was not inhibited by carbon monoxide, which implies that it was not dependent on the heme-containing microsomal drug-metabolizing system. It had a pH optimum of 8.0. Postmitochondrial liver fractions also oxidized aflatoxicol (and/or the aflatoxin B1 made from it) to at least five other metabolites that comigrated on thin-layer chromatography plates with authentic standards of aflatoxins Q1,P1,H1,M1, and B2a. None of these oxidative metabolites were formed in the presence of carbon monoxide. We also report on the in vitro reduction of aflatoxin B1 to aflatoxicol by the cytosol fractions from eight species. Most active in this regard were rabbit and trout preparations, while this activity was almost absent in the guinea pig. Preparations from humans and four other species were intermediate between these extremes.
D000348:Aflatoxins / Q000378:metabolism*; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D006224:Cricetinae; D003600:Cytosol / Q000201:enzymology; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D000882:Haplorhini; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D014337:Trout
D000348:Aflatoxins; C012170:aflatoxicol; D010088:Oxidoreductases