| Inhibition of adrenocortical cytochrome P-450scc by (20R)-20-phenyl-5-pregnene-3 beta,20-diol. | |
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MedLine Citation:
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PMID: 6687591 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The effects of the cholesterol analogue, (20R)-20-phenyl-5-pregnene-3 beta,20-diol (20-PPD), on the catalytic and spectral properties of purified bovine adrenocortical cytochrome P-450scc were investigated. In contrast to results with cholesterol and (20R)-20-hydroxycholesterol, no conversion of 20-PPD to pregnenolone could be detected; instead, 20-PPD was found to be a potent inhibitor of cytochrome P-450scc. Kinetic analyses showed that the inhibition is reversible and competitive with respect to cholesterol with an apparent Ki = 30nM. Spectral binding studies with ferricytochrome P-450scc showed that 20-PPD formed a 1:1 complex with the enzyme, having an absorption spectrum similar to that produced by (20R)-20-hydroxycholesterol. These results indicate that 20-PPD binds with very high affinity to the substrate site on cytochrome P-450scc. The finding that the phenyl side chain is readily accommodated suggests the presence in this site of an open pocket which may be normally occupied by C-22 to C-27 of the cholesterol side chain. |
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Authors:
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L E Vickery; J T Kellis |
Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 258 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 1983 Mar |
Date Detail:
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Created Date: 1983-05-05 Completed Date: 1983-05-05 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 3832-6 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adrenal Cortex
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metabolism* Animals Binding Sites Cattle Cholesterol Side-Chain Cleavage Enzyme / antagonists & inhibitors Cytochrome P-450 Enzyme System / antagonists & inhibitors* Kinetics Mitochondria / metabolism Models, Molecular Pregnenes / pharmacology* Protein Conformation Spectrophotometry |
| Grant Support | |
ID/Acronym/Agency:
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AM 1005/AM/NIADDK NIH HHS; AM 30109/AM/NIADDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/20-phenyl-5-pregnene-3 beta,20-diol; 0/Pregnenes; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.15.6/Cholesterol Side-Chain Cleavage Enzyme |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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