Effect of vitamin A deficiency on hepatic microsomal and colon mucosal mixed function oxidase. IV--Influence on aflatoxin B1 metabolism, ethylmorphine and epoxide hydrase activity.
Male, weanling rats, divided into two groups were maintained for 45 days on a corn-based diet containing 5 mg vitamin A palmitate per kg diet (Group 1, normal animals) and without the vitamin (Group 2, dificient animals). Fifteen hours after the last feeding, the animals were decapitated and liver microsomes and colon mucosal epithelial homogenates were prepared and used to investigate the relative activities of the mixed function oxidase (MFO) and epoxide hydrase (EH) enzyme systems. The sequential metabolism of aflatoxin B1 (AFB1) and its epoxide AFBepox) product, respectively, were also estimated by measuring apparent maximal velocities (Vmax) and Michaelis constants (Km) for ethylmorphine (EM) N-demethylase and styrene oxide hydratase. The Vmax data indicated that MFO activity in the liver and colon was not rate-limiting in the two groups of animals but the reverse were observed with calculated reaction rates at concentrations above (0,03 mM) for EM N-demethylase only. In both organs, styrene oxide hydratase depict calculated reaction rates which are not rate-limiting for all the concentration range (0,001 to 3,00 mM). If these reaction rates are applied to AFB1 metabolism, it may be concluded that MFO and not epoxide hydrase (EH) activity is a critical agent under vitamin A deficiency in AFB1 toxicity and/or carcinogenesis. Measurements of AFT1 metabolism both in terms of substrate disappearance and product formation do not confirm this observation except for the production of AFR0 and compounds of unknown structure at the origin which may embody the critical factor(s) that promotes colon carcinogenesis under vitamin A deficiency.
D000348:Aflatoxins / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D003106:Colon / Q000201:enzymology; D004851:Epoxide Hydrolases / Q000378:metabolism*; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism*; D005247:Feeding Behavior; D007413:Intestinal Mucosa / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D051381:Rats; D014802:Vitamin A Deficiency / Q000201:enzymology*
D000348:Aflatoxins; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D010089:Oxidoreductases, N-Demethylating; D005037:Ethylmorphine-N-Demethylase; D004851:Epoxide Hydrolases