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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
1977-2-24
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pubmed:abstractText |
1. Treatment of liver microsomal fraction with 0.03-0.12% sodium deoxycholate and 0.005-0.06 mM carbonyl cyanide m-chlorophenylhydrazone decreases phospholipid-dependent hydrophobicity of the microsomal membrane, assayed by the kinetics of 8-anilinonaphthalene-1-sulphonate binding and ethyl isocyanide difference spectra. 2. Sodium deoxycholate at a concentration of 0.01% lacks its detergent properties, but competitively inhibits aminopyrine binding and activates the initial rate of NADPH-cytochrome P-450 reductase. In the presence of 0.03-0.09% sodium deoxycholate the rate-limiting factor in p-hydroxylation of aniline is the content of cytochrome P-450. and that for N-demethylation of aminopyrine is the activity of NADPH-cytochrome P-450 reductase. 3. Carbonyl cyanide m-chlorophenylhydrazone has no effect on the binding and metabolism of aniline; investigation of its inhibiting effect on aminopyrine N-demethylase established that the rate-limiting reaction is the dissociation of the enzyme-substrate complex in the microsomal preparations. 4. In the mechanism of action of carbonyl cyanide m-chlorophenylhydrazone the key step may be the electrostatic interaction of its protonated form and one of the forms of activated oxygen at the catalytic centre of cytochrome P-450. 5. at least two different phospholipid-dependent hydrophobic zones are assumed to exist in the microsomal membrane, both coupled with cytochrome P-450. One of them reveals selective sensitivity to the protonation action of carbonyl cyanide m-chlorophenylhydrazone and contains the 'binding protein' for type I substrates and NADPH-cytochrome P-450 reductase; the other contains the cytochrome P-450 haem group and binding sites for type II substrates.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-1126002,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-1149738,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-13105648,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-13717560,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-13945466,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-13953668,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-14209972,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-14486217,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-4120344,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-4153940,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-4173846,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-4291137,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-4292159,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-4309361,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-4335189,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-4354130,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-4382749,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-4393962,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-4395592,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-4400999,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-4407522,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-4532475,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-4609003,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-4650613,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-5117524,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-5126906,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-5150143,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-5367942,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-5497715,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-5552249,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-5587592,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-5690774,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-5745914,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-5803388,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-6040018,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12746-813776
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Aminopyrine,
http://linkedlifedata.com/resource/pubmed/chemical/Aminopyrine N-Demethylase,
http://linkedlifedata.com/resource/pubmed/chemical/Aniline Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Anilino Naphthalenesulfonates,
http://linkedlifedata.com/resource/pubmed/chemical/Carbonyl Cyanide m-Chlorophenyl...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyanides,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome Reductases,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxycholic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Hemeproteins,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH-Ferrihemoprotein Reductase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitriles
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0264-6021
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
160
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
75-83
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:12746-Aminopyrine,
pubmed-meshheading:12746-Aminopyrine N-Demethylase,
pubmed-meshheading:12746-Aniline Compounds,
pubmed-meshheading:12746-Anilino Naphthalenesulfonates,
pubmed-meshheading:12746-Animals,
pubmed-meshheading:12746-Carbonyl Cyanide m-Chlorophenyl Hydrazone,
pubmed-meshheading:12746-Cyanides,
pubmed-meshheading:12746-Cytochrome P-450 Enzyme System,
pubmed-meshheading:12746-Cytochrome Reductases,
pubmed-meshheading:12746-Deoxycholic Acid,
pubmed-meshheading:12746-Hemeproteins,
pubmed-meshheading:12746-Hydrogen-Ion Concentration,
pubmed-meshheading:12746-Kinetics,
pubmed-meshheading:12746-Male,
pubmed-meshheading:12746-Microsomes, Liver,
pubmed-meshheading:12746-NADPH-Ferrihemoprotein Reductase,
pubmed-meshheading:12746-Nitriles,
pubmed-meshheading:12746-Protein Binding,
pubmed-meshheading:12746-Rats
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pubmed:year |
1976
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pubmed:articleTitle |
Mechanism of inhibition by carbonyl cyanide m-chlorophenylhydrazone and sodium deoxycholate of cytochrome P-450-catalysed hepatic microsomal drug metabolism.
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pubmed:publicationType |
Journal Article
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