Studies on the substrate-binding sites of liver microsomal cytochrome P-448.
The interaction of substrates of the microsomal mixed-function oxidases with cytochromes P-450 and P-448 was investigated by using liver microsomes from rats pretreated with phenobarbital or 3-methylcholanthrene, and with purified forms of the cytochromes isolated from rabbit liver. The two forms of the cytochrome have different substrate specificities; cytochrome P-450 has one type 1 substrate-binding site that can accommodate a large variety of substrates, but in contrast cytochrome P-448 may possess two type 1 substrate-binding sites, one of which is different to that of cytochrome P-450 in that it shows a specificity for substrates such as safrole and 9-hydroxy-ellipticine. These findings explain why the two forms of the cytochrome have different substrate specificities and play contrasting roles in the activation and deactivation of xenobiotics.
D000818:Animals; D001589:Benzphetamine / Q000378:metabolism; D001665:Binding Sites; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003580:Cytochromes / Q000378:metabolism*; D004611:Ellipticines / Q000378:metabolism; D005449:Fluorenes / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012451:Safrole / Q000378:metabolism; D013053:Spectrophotometry; D013379:Substrate Specificity
D003580:Cytochromes; D004611:Ellipticines; D005449:Fluorenes; D001589:Benzphetamine; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; C008009:9-hydroxyellipticine; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D012451:Safrole; D010634:Phenobarbital