| pubmed-article:3017933 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:3017933 | lifeskim:mentions | umls-concept:C1882726 | lld:lifeskim |
| pubmed-article:3017933 | lifeskim:mentions | umls-concept:C0010798 | lld:lifeskim |
| pubmed-article:3017933 | lifeskim:mentions | umls-concept:C1979928 | lld:lifeskim |
| pubmed-article:3017933 | lifeskim:mentions | umls-concept:C0441712 | lld:lifeskim |
| pubmed-article:3017933 | lifeskim:mentions | umls-concept:C0045948 | lld:lifeskim |
| pubmed-article:3017933 | pubmed:issue | 25 | lld:pubmed |
| pubmed-article:3017933 | pubmed:dateCreated | 1986-10-15 | lld:pubmed |
| pubmed-article:3017933 | pubmed:abstractText | The mechanism by which 2-bromo-4'-nitroacetophenone (BrNAP) inactivates cytochrome P-450c, which involves alkylation primarily at Cys-292, is shown in the present study to involve an uncoupling of NADPH utilization and oxygen consumption from product formation. Alkylation of cytochrome P-450c with BrNAP markedly stimulated (approximately 30-fold) its rate of anaerobic reduction by NADPH-cytochrome P-450 reductase, as determined by stopped flow spectroscopy. This marked stimulation in reduction rate is highly unusual in that Cys-292 is apparently not part of the heme- or substrate-binding site, and its alkylation by BrNAP does not cause a low spin to high spin state transition in cytochrome P-450c. Under aerobic conditions the rapid oxidation of NADPH catalyzed by alkylated cytochrome P-450c was associated with rapid reduction of molecular oxygen to hydrogen peroxide via superoxide anion. The intermediacy of superoxide anion, formed by the one-electron reduction of molecular oxygen, established that alkylation of cytochrome P-450c with BrNAP uncouples the catalytic cycle prior to introduction of the second electron. The generation of superoxide anion by decomposition of the Fe2+ X O2 complex was consistent with the observations that, in contrast to native cytochrome P-450c, alkylated cytochrome P-450c failed to form a 430 nm absorbing chromophore during the metabolism of 7-ethoxycoumarin. Alkylation of cytochrome P-450c with BrNAP did not completely uncouple the catalytic cycle such that 5-20% of the catalytic activity remained for the alkylated cytochrome compared to the native protein depending on the substrate assayed. The uncoupling effect was, however, highly specific for cytochrome P-450c. Alkylation of nine other rat liver microsomal cytochrome P-450 isozymes with BrNAP caused little or no increase in hydrogen peroxide formation in the presence of NADPH-cytochrome P-450 reductase and NADPH. | lld:pubmed |
| pubmed-article:3017933 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:3017933 | pubmed:language | eng | lld:pubmed |
| pubmed-article:3017933 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:3017933 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:3017933 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:3017933 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:3017933 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:3017933 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:3017933 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:3017933 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:3017933 | pubmed:month | Sep | lld:pubmed |
| pubmed-article:3017933 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:3017933 | pubmed:author | pubmed-author:LevinWW | lld:pubmed |
| pubmed-article:3017933 | pubmed:author | pubmed-author:ShivelyJ EJE | lld:pubmed |
| pubmed-article:3017933 | pubmed:author | pubmed-author:JerinaD MDM | lld:pubmed |
| pubmed-article:3017933 | pubmed:author | pubmed-author:ThomasP EPE | lld:pubmed |
| pubmed-article:3017933 | pubmed:author | pubmed-author:ParkinsonAA | lld:pubmed |
| pubmed-article:3017933 | pubmed:author | pubmed-author:RyanD EDE | lld:pubmed |
| pubmed-article:3017933 | pubmed:author | pubmed-author:GorskyL DLD | lld:pubmed |
| pubmed-article:3017933 | pubmed:author | pubmed-author:SayerJ MJM | lld:pubmed |
| pubmed-article:3017933 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:3017933 | pubmed:day | 5 | lld:pubmed |
| pubmed-article:3017933 | pubmed:volume | 261 | lld:pubmed |
| pubmed-article:3017933 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:3017933 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:3017933 | pubmed:pagination | 11487-95 | lld:pubmed |
| pubmed-article:3017933 | pubmed:dateRevised | 2007-11-14 | lld:pubmed |
| pubmed-article:3017933 | pubmed:meshHeading | pubmed-meshheading:3017933-... | lld:pubmed |
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| pubmed-article:3017933 | pubmed:meshHeading | pubmed-meshheading:3017933-... | lld:pubmed |
| pubmed-article:3017933 | pubmed:meshHeading | pubmed-meshheading:3017933-... | lld:pubmed |
| pubmed-article:3017933 | pubmed:meshHeading | pubmed-meshheading:3017933-... | lld:pubmed |
| pubmed-article:3017933 | pubmed:meshHeading | pubmed-meshheading:3017933-... | lld:pubmed |
| pubmed-article:3017933 | pubmed:meshHeading | pubmed-meshheading:3017933-... | lld:pubmed |
| pubmed-article:3017933 | pubmed:meshHeading | pubmed-meshheading:3017933-... | lld:pubmed |
| pubmed-article:3017933 | pubmed:meshHeading | pubmed-meshheading:3017933-... | lld:pubmed |
| pubmed-article:3017933 | pubmed:meshHeading | pubmed-meshheading:3017933-... | lld:pubmed |
| pubmed-article:3017933 | pubmed:meshHeading | pubmed-meshheading:3017933-... | lld:pubmed |
| pubmed-article:3017933 | pubmed:year | 1986 | lld:pubmed |
| pubmed-article:3017933 | pubmed:articleTitle | Mechanism of inactivation of rat liver microsomal cytochrome P-450c by 2-bromo-4'-nitroacetophenone. | lld:pubmed |
| pubmed-article:3017933 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:3017933 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| pubmed-article:3017933 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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