Search

Mammalian adrenodoxin (Adx) has been known for many years as an essential electron mediator in mitochondrial cytochrome P450 systems. Because of its ability to support several cytochrome P450 enzymes, it is involved not only in adrenal steroid hormone biosynthesis but also in vitamin D and bile acid metabolism. Recently, Adx is increasingly gaining attention because of its potential for pharmaceutical industry and biotechnology. With human cytochromes P450 becoming important drug targets, suitable Adx-based screening systems have to be developed to test putative new drugs. Moreover, in artificial systems, Adx has been shown to functionally interact with diverse bacterial cytochromes P450 catalyzing a variety of chemically interesting reactions. Putative biotechnological applications of such Adx-containing reconstituted systems are discussed. © 2012 IUBMB IUBMB Life, 2012 [ABSTRACT FROM AUTHOR]

12α-Hydroxylation of 5β-cholestane-3α,7α-diol was studied in reconstituted systems consisting of electrophoretically homogeneous cytochrome P-450 LM4 fractions and NADPH-cytochrome P-450 reductase from rabbit liver microsomes. Cytochrome P-450 LM4 fractions were prepared from untreated, phenobarbital-treated, β-naphthoflavone-treated and starved rabbits. The purified cytochromes catalyzed 12α-hydroxylation more efficiently than the corresponding microsomes. In the reconstituted systems, carbon monoxide inhibited 12α-hydroxylation by 50-80%. The rate of 12α-hydroxylation was three to four times higher with cytochrome P-450 LM4 fractions from starved rabbits than with cytochrome P-450 LM4 fractions from untreated, phenobarbital-treated and β-naphthoflavone-treated animals. Amino acid analyses, peptide mapping experiments as well as absorption spectral and circular dichroism spectral analyses revealed physical differences between cytochrome P-450 LM4 fractions from starved animals and preparations from phenobarbital-treated animals. The results indicate the presence of a cytochrome P-450 species in the cytochrome P-450 LM4 fraction specific for 12α-hydroxylation. [ABSTRACT FROM AUTHOR]

Presents abstracts of studies on biotransformation and drug transport, presented at the Experimental Biology/International Union of Physiological Sciences 2005 congress held in San Diego, California. "Ontogeny of Brain Mdr1a Expression: Implications for Cyclosporine A Neurotoxicity in Young Children," by Philip Acott, David Worth et al.; "Regulation of the Multidrug Resistance-Associated Protein 3 by Bile Acids," by Tanya Christina McCarthy, Xiufeng Li and Christopher J. Sinal; "Differences in the Inhibition of Cytochromes P450 3A4 and 3A5 by Metabolite-Inhibitor Complex Forming Drugs," by Jason Boer, Kyle Allen et al.