دورية أكاديمية
Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation.
| العنوان: | Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation. |
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| المؤلفون: | Born SL; The Miami Valley Laboratories, Procter & Gamble, Cincinnati, Ohio, USA. stephanie.born@bms.com, Caudill D, Fliter KL, Purdon MP |
| المصدر: | Drug metabolism and disposition: the biological fate of chemicals [Drug Metab Dispos] 2002 May; Vol. 30 (5), pp. 483-7. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Pharmacology and Experimental Therapeutics, etc.] Country of Publication: United States NLM ID: 9421550 Publication Model: Print Cited Medium: Print ISSN: 0090-9556 (Print) Linking ISSN: 00909556 NLM ISO Abbreviation: Drug Metab Dispos Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Bethesda, Md., etc., American Society for Pharmacology and Experimental Therapeutics, etc.] |
| مواضيع طبية MeSH: | Cosmetics/*metabolism , Coumarins/*metabolism , Cytochrome P-450 Enzyme System/*metabolism , Microsomes/*metabolism, Animals ; Female ; Humans ; Hydroxylation ; In Vitro Techniques ; Lung/enzymology ; Lung/metabolism ; Lung/ultrastructure ; Male ; Mice ; Microsomes/enzymology ; Microsomes, Liver/enzymology ; Microsomes, Liver/metabolism ; Rats ; Rats, Inbred F344 |
| مستخلص: | Coumarin, a widely used fragrance ingredient, is a rat liver and mouse lung toxicant. Species differences in toxicity are metabolism-dependent, with injury resulting from the cytochrome P450-mediated formation of coumarin 3,4-epoxide (CE). In this study, the enzymes responsible for coumarin activation in liver and lung were determined. Recombinant human and rat CYP1A forms and recombinant human CYP2E1 readily catalyzed CE production. Coinhibition with CYP1A1/2 and CYP2E1 antibodies blocked CE formation by 38, 84, and 67 to 92% (n = 3 individual samples) in mouse, rat, and human hepatic microsomes, respectively. Although CYP1A and 2E forms seem to be the most active catalysts of CE formation in liver, studies conducted with the mechanism-based inhibitor 5-phenyl-pentyne demonstrated that CYP2F2 is responsible for up to 67% of CE formation in whole mouse lung microsomes. In contrast to the CE pathway, coumarin 3-hydroxylation is a minor product of coumarin in liver microsomes from mice, rats, and humans and is catalyzed predominately by CYP3A and CYP1A forms, confirming that CE and 3-hydroxycoumarin are formed via distinct metabolic pathways. |
| المشرفين على المادة: | 0 (Cosmetics) 0 (Coumarins) 143873-69-2 (coumarin 3,4-epoxide) 9035-51-2 (Cytochrome P-450 Enzyme System) A4VZ22K1WT (coumarin) |
| تواريخ الأحداث: | Date Created: 20020416 Date Completed: 20020912 Latest Revision: 20190607 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1124/dmd.30.5.483 |
| PMID: | 11950775 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 0090-9556 |
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| DOI: | 10.1124/dmd.30.5.483 |