{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T22:28:22Z","timestamp":1648506502570},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1976,10,15]]},"abstract":"<jats:p>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 \u2018binding protein\u2019 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.<\/jats:p>","DOI":"10.1042\/bj1600075","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T20:04:42Z","timestamp":1439237082000},"page":"75-83","update-policy":"http:\/\/dx.doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mechanism of inhibition by carbonyl cyanide <i>m<\/i>-chlorophenylhydrazone and sodium deoxycholate of cytochrome <i>P<\/i>-450-catalysed hepatic microsomal drug metabolism"],"prefix":"10.1042","volume":"160","author":[{"given":"I B","family":"Tsyrlov","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Institute of Experimental and Clinical Medicine, Academy of Medical Sciences of the U.S.S.R., Siberian Branch, Novosibirsk 630091, U.S.S.R."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O A","family":"Gromova","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Experimental and Clinical Medicine, Academy of Medical Sciences of the U.S.S.R., Siberian Branch, Novosibirsk 630091, U.S.S.R."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V V","family":"Lyakhovich","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Experimental and Clinical Medicine, Academy of Medical Sciences of the U.S.S.R., Siberian Branch, Novosibirsk 630091, U.S.S.R."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/160\/1\/75\/567371\/bj1600075.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/160\/1\/75\/567371\/bj1600075.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T13:39:36Z","timestamp":1637933976000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/160\/1\/75\/5102\/Mechanism-of-inhibition-by-carbonyl-cyanide-m"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1976,10,15]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1976,10,15]]}},"URL":"https:\/\/doi.org\/10.1042\/bj1600075","relation":{},"ISSN":["0264-6021"],"issn-type":[{"value":"0264-6021","type":"print"}],"subject":[],"published":{"date-parts":[[1976,10,15]]}}}