IMMUNOCHEMICAL CHARACTERIZATION OF STEROID HYDROXYLASES OF ADRENOCORTICAL MITOCHONDRIA - 1 - ANTIBODIES AS INHIBITORS OF CYTOCHROME P450SCC(CYP11A1) AND P450(11-BETA) (CYP11B1) ACTIVITIES

The effects of antibodies against protein components of the monooxygen ase systems of adrenocortical mitochondria on the reactions of hydroxy lation of cholesterol and 11 beta-deoxycorticosterone were investigate d in a reconstituted system containing cytochromes P450scc (CYP11A1) a nd P450(11 beta) (CYP11B1) as the terminal oxidases and the electron-t ransfer proteins adrenodoxin reductase and adrenodoxin. It has been sh own that affinity-purified antibodies to cytochromes P450scc and P450( 11 beta) are efficient modulators of the activity of these systems, an d their inhibiting effect is mainly due to interference with the inter action of heme proteins and adrenodoxin. The antibodies against polype ptide fragments of the cytochrome P450scc molecule FI (Ile(1)-Arg(256) ), F2 (Asn(257)-Ala(481)), and F3 (Asn(257)-Arg(399)) were used to dem onstrate that the interaction of heme protein with adrenodoxin has a m ultisite character and involves regions located in the N- and C-termin al sequences of cytochrome P450scc.