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Clin Exp Pharmacol Physiol

Title:		Cytochromes P-450 in steroidogenesis: are these enzymes more specific than those of drug metabolism?
Author(s):		Hall PF;
Address:		"Department of Endocrinology, University of New South Wales, Kensington, Australia"
Journal Title:		Clin Exp Pharmacol Physiol
Year:		1989
Volume:		16
Issue:		6
Page Number:		485 - 489
DOI:		10.1111/j.1440-1681.1989.tb01592.x
ISSN/ISBN:		0305-1870 (Print) 0305-1870 (Linking)
Abstract:		"1. In contrast to drug-metabolizing cytochromes P-450, the corresponding steroidogenic enzymes appear to be highly specific with respect to substrates, reactions catalysed, and the sites in the substrate molecule that are attacked. 2. Recent studies have shown that important exceptions to this generalization are encountered. 3. The conversion of 11-deoxycorticosterone to aldosterone requires three enzymatic reactions, the last of which (aldehyde synthetase), like the first two, requires a P-450 mono-oxygenation. The involvement of P-450 in this third step (from alcohol to aldehyde) was demonstrated by photochemical action spectra and determination of stoichiometry. The three reactions were shown to be catalysed by a single enzyme as demonstrated by immunoprecipitation and the use of a homogenous enzyme. 4. The conversion of pregnenolone and progesterone to the corresponding delta 16-C19 steroids, which are pheromones, is catalysed by a cytochrome P-450 that also catalyses the conversion of progesterone to androstenedione (that is, C21 side-chain cleavage; hydroxylase/lyase). The synthesis of the delta 16 compounds requires cytochrome b5. 5. The conversion of testosterone and epitestosterone to androstenedione is catalysed by P-450b. Studies of kinetic isotope effects using deuterium and 18O2 show that P-450b catalyses this reaction with epitestosterone via the formation of a gem diol, whereas, with testosterone as substrate, one-third of the product is formed via the same mechanism while the remainder results from the mechanism described as dual hydrogen abstraction"
Keywords:		Animals Cytochrome P-450 Enzyme System/*metabolism Humans Pharmaceutical Preparations/*metabolism Steroids/*biosynthesis Substrate Specificity;
Notes:		"MedlineHall, P F eng Review Australia 1989/06/01 Clin Exp Pharmacol Physiol. 1989 Jun; 16(6):485-9. doi: 10.1111/j.1440-1681.1989.tb01592.x"