| pubmed-article:15797239 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15797239 | lifeskim:mentions | umls-concept:C0035820 | lld:lifeskim |
| pubmed-article:15797239 | lifeskim:mentions | umls-concept:C0205103 | lld:lifeskim |
| pubmed-article:15797239 | lifeskim:mentions | umls-concept:C0010762 | lld:lifeskim |
| pubmed-article:15797239 | lifeskim:mentions | umls-concept:C0311400 | lld:lifeskim |
| pubmed-article:15797239 | lifeskim:mentions | umls-concept:C1704241 | lld:lifeskim |
| pubmed-article:15797239 | lifeskim:mentions | umls-concept:C0644298 | lld:lifeskim |
| pubmed-article:15797239 | pubmed:issue | 2 | lld:pubmed |
| pubmed-article:15797239 | pubmed:dateCreated | 2005-3-30 | lld:pubmed |
| pubmed-article:15797239 | pubmed:abstractText | The inactivation of cytochrome P450 enzymes by cyclopropylamines has been attributed to a mechanism involving initial one-electron oxidation at nitrogen followed by scission of the cyclopropane ring leading to covalent modification of the enzyme. Herein, we report that in liver microsomes N-cyclopropylbenzylamine (1) and related compounds inactivate P450 to a large extent via formation of metabolic intermediate complexes (MICs) in which a nitroso metabolite coordinates tightly to the heme iron, thereby preventing turnover. MIC formation from 1 does not occur in reconstituted P450 systems with CYP2B1/2, 2C11 or 2E1, or in microsomes exposed to gentle heating to inactivate the flavin-containing monooxygenase (FMO). In contrast, N-hydroxy-N-cyclopropylbenzylamine (3) and N-benzylhydroxylamine (4) generate MICs much faster than 1 in both reconstituted and microsomal systems. MIC formation from nitrone 5 (PhCH = N(O)cPr) is somewhat faster than from 1, but very much faster than the hydrolysis of 5 to a primary hydroxylamine. Thus the major overall route from 1 to a P450 MIC complex would appear to involve FMO oxidation to 3, further oxidation by P450 and/or FMO to nitrone 5' (C2H4C = N(O)CH2Ph), hydrolysis to 4, and P450 oxidation to alpha-nitrosotoluene as the precursor to oxime 2 and the major MIC from 1. | lld:pubmed |
| pubmed-article:15797239 | pubmed:language | eng | lld:pubmed |
| pubmed-article:15797239 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15797239 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:15797239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15797239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15797239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15797239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15797239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15797239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15797239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15797239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15797239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15797239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15797239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15797239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15797239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15797239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15797239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15797239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15797239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15797239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15797239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15797239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15797239 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15797239 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15797239 | pubmed:month | Apr | lld:pubmed |
| pubmed-article:15797239 | pubmed:issn | 0003-9861 | lld:pubmed |
| pubmed-article:15797239 | pubmed:author | pubmed-author:HanzlikRobert... | lld:pubmed |
| pubmed-article:15797239 | pubmed:author | pubmed-author:CernyMatthew... | lld:pubmed |
| pubmed-article:15797239 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15797239 | pubmed:day | 15 | lld:pubmed |
| pubmed-article:15797239 | pubmed:volume | 436 | lld:pubmed |
| pubmed-article:15797239 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15797239 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15797239 | pubmed:pagination | 265-75 | lld:pubmed |
| pubmed-article:15797239 | pubmed:dateRevised | 2008-11-21 | lld:pubmed |
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| pubmed-article:15797239 | pubmed:year | 2005 | lld:pubmed |
| pubmed-article:15797239 | pubmed:articleTitle | Cyclopropylamine inactivation of cytochromes P450: role of metabolic intermediate complexes. | lld:pubmed |
| pubmed-article:15797239 | pubmed:affiliation | Department of Medicinal Chemistry, University of Kansas, Lawrence, KS, USA. | lld:pubmed |
| pubmed-article:15797239 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:15797239 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:15797239 | lld:pubmed |
