title: Regio-selectivity of purified forms of rabbit liver microsomal cytochrome P-450 in the metabolism of benzo(a)pyrene, n-hexane and 7-ethoxyresorufin.
abstract: The specificity of electrophoretically homogeneous preparations of rabbit liver microsomal cytochrome P-450LM2-4 towards oxygenation of n-hexane, 7-ethoxyresorufin and benzo(a)pyrene was examined using a reconstituted system consisting of cytochrome P-450, NADPH-cytochrome P-450 reductase and dilauroylphosphatidylcholine. Epoxide hydrase was included when benzo(a)pyrene was used as substrate. Cytochrome P-450LM2 was most active in n-hexane and benzo(a)pyrene oxygenation especially with regard to the formation of 2-hexanol, B(a)P-4,5-dihydrodiol and B(a)P-phenol metabolites. 7-Ethoxyresorufin was, however, a very poor substrate for cytochrome P-450LM2. Cytochrome P-450LM3 had less activity towards the investigated substrates while cytochrome P-450LM4 preferentially formed 2- and 3-hexanol, resorufin and B(a)P-9,10-dihydrodiol. Cytochrome P-450LM4 isolated after pretreatment with 3-methylcholanthrene or phenobarbital showed roughly the same characteristics except in the formation of 1-hexanol where cytochrome P-450LM4 isolated after phenobarbital treatment was the most effective. The formation of B(a)P-4,5- and -9,10-dihydrodiols was greatly increased by incorporation of epoxide hydrase. Our results indicate a certain specificity of the different forms of cytochrome P-450 in the liver microsomes although some overlap in activities was observed.
mesh_terms: D000818:Animals; D001580:Benzopyrenes / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000494:pharmacology*; D004851:Epoxide Hydrolases / Q000494:pharmacology; D006586:Hexanes / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D010078:Oxazines / Q000378:metabolism*; D011817:Rabbits; D013379:Substrate Specificity
chemical_list: D001580:Benzopyrenes; D006586:Hexanes; D010078:Oxazines; C007649:ethoxyresorufin; D003577:Cytochrome P-450 Enzyme System; D004851:Epoxide Hydrolases