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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1989-6-29
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pubmed:abstractText |
Rates of N-demethylation of N,N-dimethylaniline and of eight meta- or para-substituted N,N-dimethylanilines by rat liver cytochrome P-450PB-B (P-450) were determined under conditions where oxidation was supported by iodosylbenzene or NADPH-P-450 reductase. The rates of dimethylaniline oxidation were found to correlate with the substrate oxidation-reduction potential within each series of substrates supported by a particular oxygen activation protocol; the kcat for each substrate studied was approximately 20-fold faster in the iodosylbenzene-supported system relative to the NADPH-P-450 reductase supported system. Since the N-demethylation of amines is believed to proceed via an initial electron-transfer step, a kinetic scheme for P-450 was proposed that enabled evaluation of the data according to theoretical treatments that correlate rates of electron transfer with extrakinetic parameters. In these analyses, the data could be fitted to the Rehm-Weller and Agmon-Levine equations, providing lambda values (for the energetics of enzyme-substrate reorganization) of 22-26 kcal mol-1 and apparent E1/2 (oxidation-reduction potentials) of 1.7-2.0 V (vs saturated calomel) for the oxidized enzyme. The apparent E1/2 for the enzyme is composed of contributions from the intrinsic potential of the active prosthetic core of the enzyme, the Fe = O - porphyrin species, and a coulombic factor that is a function of the charge-separated radical anion/radical cation pair produced upon electron transfer.(ABSTRACT TRUNCATED AT 250 WORDS)
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Aniline Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/Iodobenzenes,
http://linkedlifedata.com/resource/pubmed/chemical/N,N-dimethylaniline,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH-Ferrihemoprotein Reductase,
http://linkedlifedata.com/resource/pubmed/chemical/iodosobenzene
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0006-2960
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
28
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2071-7
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:2497774-Aniline Compounds,
pubmed-meshheading:2497774-Animals,
pubmed-meshheading:2497774-Catalysis,
pubmed-meshheading:2497774-Chemistry, Physical,
pubmed-meshheading:2497774-Cytochrome P-450 Enzyme System,
pubmed-meshheading:2497774-Iodobenzenes,
pubmed-meshheading:2497774-Methylation,
pubmed-meshheading:2497774-NADPH-Ferrihemoprotein Reductase,
pubmed-meshheading:2497774-Oxidation-Reduction,
pubmed-meshheading:2497774-Physicochemical Phenomena,
pubmed-meshheading:2497774-Rats,
pubmed-meshheading:2497774-Thermodynamics
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pubmed:year |
1989
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pubmed:articleTitle |
Oxidation of substituted N,N-dimethylanilines by cytochrome P-450: estimation of the effective oxidation-reduction potential of cytochrome P-450.
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pubmed:affiliation |
Department of Chemistry, University of Virginia, Charlottesville 22901.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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