دورية أكاديمية
Cytochrome P450-dependent catabolism of vitamin K: ω-hydroxylation catalyzed by human CYP4F2 and CYP4F11.
| العنوان: | Cytochrome P450-dependent catabolism of vitamin K: ω-hydroxylation catalyzed by human CYP4F2 and CYP4F11. |
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| المؤلفون: | Edson KZ; Department of Medicinal Chemistry and ‡Department of Pharmaceutics, School of Pharmacy at the University of Washington , Box 357610, Seattle, Washington 98105, United States., Prasad B, Unadkat JD, Suhara Y, Okano T, Guengerich FP, Rettie AE |
| المصدر: | Biochemistry [Biochemistry] 2013 Nov 19; Vol. 52 (46), pp. 8276-85. Date of Electronic Publication: 2013 Nov 07. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 0370623 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4995 (Electronic) Linking ISSN: 00062960 NLM ISO Abbreviation: Biochemistry Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, American Chemical Society. |
| مواضيع طبية MeSH: | Cytochrome P-450 Enzyme System/*metabolism , Vitamin K 2/*analogs & derivatives, Cytochrome P-450 CYP4A/metabolism ; Cytochrome P450 Family 4 ; Humans ; Hydroxylation ; Kinetics ; Microsomes, Liver/enzymology ; Vitamin K 2/metabolism |
| مستخلص: | Vitamin K plays an essential role in many biological processes including blood clotting, maintenance of bone health, and inhibition of arterial calcification. A menaquinone form of vitamin K, MK4, is increasingly recognized for its key roles in mitochondrial electron transport, as a ligand for the nuclear receptor SXR, which controls the expression of genes involved in transport and metabolism of endo- and xenobiotics, and as a pharmacotherapeutic in the treatment of osteoporosis. Although cytochrome P450 (CYP) 4F2 activity is recognized as an important determinant of phylloquinone (K1) metabolism, the enzymes involved in menaquinone catabolism have not been studied previously. CYP4F2 and CYP4F11 were expressed and purified and found to be equally efficient as in vitro catalysts of MK4 ω-hydroxylation. CYP4F2, but not CYP4F11, catalyzed sequential metabolism of MK4 to the ω-acid without apparent release of the intermediate aldehyde. The ω-alcohol could also be metabolized to the acid by microsomal NAD(+)-dependent alcohol and aldehyde dehydrogenases. LC-MS/MS analysis of trypsinized human liver microsomes (using a surrogate peptide approach) revealed the mean concentrations of CYP4F2 and CYP4F11 to be 14.3 and 8.4 pmol/mg protein, respectively. Microsomal MK4 ω-hydroxylation activities correlated with the CYP4F2 V433M genotype but not the CYP4F11 D446N genotype. Collectively, these data expand the lexicon of vitamin K ω-hydroxylases to include the 'orphan' P450 CYP4F11 and identify a common variant, CYP4F2 (rs2108622), as a major pharmacogenetic variable influencing MK4 catabolism. |
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| معلومات مُعتمدة: | U01 GM092676 United States GM NIGMS NIH HHS; R37 CA090426 United States CA NCI NIH HHS; R01 GM109743 United States GM NIGMS NIH HHS; R01 GM068797 United States GM NIGMS NIH HHS; U01 GM92676 United States GM NIGMS NIH HHS |
| المشرفين على المادة: | 11032-49-8 (Vitamin K 2) 27Y876D139 (menatetrenone) 9035-51-2 (Cytochrome P-450 Enzyme System) EC 1.14.14.1 (Cytochrome P450 Family 4) EC 1.14.14.78 (CYP4F11 protein, human) EC 1.14.14.78 (CYP4F2 protein, human) EC 1.14.15.3 (Cytochrome P-450 CYP4A) |
| تواريخ الأحداث: | Date Created: 20131022 Date Completed: 20140121 Latest Revision: 20211021 |
| رمز التحديث: | 20240829 |
| مُعرف محوري في PubMed: | PMC3900248 |
| DOI: | 10.1021/bi401208m |
| PMID: | 24138531 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1520-4995 |
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| DOI: | 10.1021/bi401208m |