tailieunhanh - Báo cáo khoa học: An alternative pathway of vitamin D2metabolism Cytochrome P450scc (CYP11A1)-mediated conversion to 20-hydroxyvitamin D2and 17,20-dihydroxyvitamin D2

We report an alternative, hydroxylating pathway for the metabolism of vitamin D2 in a cytochrome P450 side chain cleavage (P450scc; CYP11A1) reconstituted system. NMR analyses identified solely 20-hydroxyvitamin D2and 17,20-dihydroxyvitamin D2derivatives. 20-Hydroxyvitamin D2was produced at a rate of molÆmin )1 Æmol )1 P450scc, and 17,20-dihydroxy-vitamin D2 was produced at a rate of molÆmin )1 Æmol )1 . | ềFEBS Journal An alternative pathway of vitamin D2 metabolism Cytochrome P450SCC CYP11A1 -mediated conversion to 20-hydroxyvitamin D2 and 17 20-dihydroxyvitamin D2 Andrzej Slominski1 Igor Semak2 Jacobo Wortsman3 Jordan Zjawiony4 Wei Li5 Blazej Zbytek1 if and Robert C. Tuckey6 1 Department of Pathology and Laboratory Medicine University of Tennessee Health Science Center Memphis TN USA 2 Department of Biochemistry Belarus State University Minsk Belarus 3 Department of Medicine Southern Illinois University Springfield IL USA 4 Department of Pharmacognosy University of Mississippi TN USA 5 Department of PharmaceuticalSciences University of Tennessee Health Science Center Memphis TN USA 6 Department of Biochemistry and Molecular Biology Schoolof Biomedical Biomolecular and ChemicalScience The University of Western Australia Crawley Australia Keywords cytochrome P450scc keratinocytes skin vitamin D2 Correspondence A. Slominski Department of Pathology and Laboratory Medicine University of Tennessee Health Science Center 930 Madison Avenue RM525 Memphis TN 38163 USA Fax 1 901 448 6979 Tel 1 901 448 3741 E-mail aslominski@ Received 16 March 2006 revised 24 April 2006 accepted 2 May 2006 doi We report an alternative hydroxylating pathway for the metabolism of vitamin D2 in a cytochrome P450 side chain cleavage P450scc CYP11A1 reconstituted system. NMR analyses identified solely 20-hydroxyvitamin D2 and 17 20-dihydroxyvitamin D2 derivatives. 20-Hydroxyvitamin D2 was produced at a rate of mol-min_1-mol-1 P450scc and 17 20-dihydroxy-vitamin D2 was produced at a rate of mol-min_1-mol-1. In adrenal mitochondria vitamin D2 was metabolized to six monohydroxy products. Nevertheless aminoglutethimide a P450scc inhibitor inhibited this adrenal metabolite formation. Initial testing of metabolites for biological activity showed that similar to vitamin D2 20-hydroxyvitamin D2 and 17 20-dihydroxyvitamin D2 inhibited DNA synthesis in .