The superfamily of hemoproteins, termed cytochrome P-450, catalyze the oxidative biotransformation of a wide variety of endogenous and exogenous organic compounds. Many of the steps for the conversion of cholesterol to androgens and estrogens and then to bile acids, as well as the omega oxidation of medium chainlength fatty acids and prostaglandins, involve unique cytochromes P-450. Many xenobiotics, such as drugs, carcinogenic chemicals, pesticides, etc., are metabolically converted by atmospheric oxygen activated during the reduction-oxidation cycling of various cytochromes P-450.
This laboratory is concerned with better understanding the regulation of function of the different cytochromes P-450. Using spectrophotometric methods to monitor the steady-state concentration of the hemoproteins as well as hplc techniques for tracking rates of metabolism, studies are directed toward better describing the geometric proximity of membrane-bound cytochromes P-450, as they interact with a flavoprotein dehydrogenase, and the influence of the lipid milieu on the comparative activities of cytochrome P-450 as an oxygenase, oxidase or peroxygenase (peroxidase). Presently, emphasis is directed toward understanding the process of alkane oxidation reactions, in particular the omega oxidation of fatty acids induced in liver by hypolipidemic drugs, and the multiple pathways of C19-steroid hormone metabolism by unique cytochromes P-450 of liver microsomes.
RESEARCH INTERESTS
History of Biological Electron Transport Systems
History of Biochemical reactions Related to Steroid Hormone Biosynthesis
RECENT PUBLICATIONS
Gilep, A.A., Huryeva, I.V., Guryev, O.L., Usanov, S.A. and Estabrook, R.W., "Cloning and heterologous expression of the cDNA encoding the cytochrome P459 steroid 17alpha-hydroxylase/17,20 lyase from bison." GeneBank, AF292526 2000
Usanov, S.A., Graham, S.E., Lepesheva, G.I., Azeva, T.N., Strushkevish, N.V., Gilep, A.A., Estabrook, R.W., and Peterson, J.A., "Probing the Interaction of Bovine Cytochrome P450scc (CYP11A1) with Adrenodoxin: Evaluating Site-directed Mutations by Molecular Modeling." Biochemistry, 41:8310-8320, 2002
Gilep, A.A., Guryev, O.L., Usanov, S.A., and Estabrook, R.W., "An Enzymatically Active Chimeric Protein Containing the Hydrophilic Form of NADPH-Cytochrome P450 Reductase Fused to the Membrane-binding Domain of Cytochrome b5." Biochem. Biophys. Res. Commun., 284:937-941, 2001
Gilep, A.A., Guryev, O.L., Usanov, S.A., and Estabrook, R.W., "Apo-cytochrome b5 as an Indicator of Changes in Heme Accessability: Preliminary Studies with Cytochrome P450 3A4." J. Inorganic Biochem., 87:237-244, 2001
Wilson, J.D., Auchus, R.J., Leihy, M.W., Guryev, O.L., Estabrook, R.W., Osborn, S.M., Shaw G., and Renfree, M.B., "5(alpha)-Androstane-3(alpha), 17(beta)-Diol is formed in Tammar Wallaby Pouch Young Testes by a Pathway involving 5(alpha)-Pregnane-3(alpha), 17(alpha)-Diol-20-One as a Key Intermediate." Endocrinology, 144:575-580, 2002
SIGNIFICANT PUBLICATIONS
Estabrook, R.W., and Holowinsky, A., "Studies on the content and organization of the respiratory enzymes of mitochondria." J. Biophys, Biochem. Cytol., 9:19-28, 1961
Cooper, D.Y., Levin, S., Narasimhulu, S., Rosenthal, O. and Estabrook, R.W., "Photochemical action spectrum of the terminal oxidase of mixed function oxidase systems." Science, 147:400-402, 1965
Fisher, C.W., Caudle, D.L., Martin-Wixtrom, C., Quattrochi, L.C., Tukey, R.H., Waterman, M.R., and Estabrook, R.W., "High level expression of functional human cytochrome P450 1A2 in Escherica coli." FASEB J., 6:759-764, 1992
Estabrook,R.W., "The low temperature spectra of hemoproteins. I. Apparatus and its application to a study of cytochrome c." J. Biol. Chem., 223:781-794, 1956
Kuthan, H., Tsuji, H., Graf, H., Ullrich, V., Werringloer, J., and Estabrook, R.W., "Generation of superoxide anion as a source of hydrogen peroxide in a reconstituted monooxygenase system." FEBS Letters, 91:343-345, 1978
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