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Am J Physiol Endocrinol Metab 288: E753-E760, 2005. First published December 7, 2004; doi:10.1152/ajpendo.00201.2004
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Characterization of recombinant CYP2C11: a vitamin D 25-hydroxylase and 24-hydroxylase

Mehrdad Rahmaniyan,1 Kennerly Patrick,2 and Norman H. Bell1

Departments of 1Medicine and 2Pharmaceutical Sciences, Medical University of South Carolina, Strom Thurmond Research Building, Charleston, South Carolina

Submitted 7 May 2004 ; accepted in final form 23 November 2004

Studies were performed to further characterize the male-specific hepatic recombinant microsomal vitamin D 25-hydroxlase CYP2C11, expressed in baculovirus-infected insect cells, and determine whether it is also a vitamin D 24-hydroxylase. 25- and 24-hydroxylase activities were compared with those of 10 other recombinant hepatic microsomal cytochrome P-450 enzymes expressed in baculovirus-infected insect cells. Each of them 25-hydroxylated vitamin D2, vitamin D3, 1{alpha}-hydroxyvitamin D2 (1{alpha}OHD2), and 1{alpha}-hydroxyvitamin D3 (1{alpha}OHD3). CYP2C11 had the greatest activity with these substrates, except vitamin D3, which had the same activity as four of the other enzymes. The descending order of 25-hydroxylation by CYP2C11 was 1{alpha}OHD3 > 1{alpha}OHD2 > vitamin D2 > vitamin D3. Each of the recombinant cytochrome P-450 enzymes 24-hydroxylated 1{alpha}OHD2. CYP2C11 had the greatest activity. 24-Hydroxylation of 1{alpha}OHD3 was very low, and there was none with vitamin D3. Only CYP2C11 24-hydroxylated vitamin D2. Structures of vitamin D metabolites, including 24-hydroxyvitamin D2, 1,24(S)-dihydroxyvitamin D2, and 1,24-dihydroxyvitamin D3, were confirmed by HPLC and gas chromatography retention times and characteristic mass spectrometric fragmentation patterns. In male rats, hypophysectomy significantly reduced body weight, liver weight, hepatic CYP2C11 mRNA expression, and 24- and 25-hydroxylation of 1{alpha}OHD2. Expression of CYP2J3 and CYP2R1 mRNA did not change. In male rat hepatocytes, CYP2C11 mRNA expression and 24- and 25-hydroxylation were significantly reduced after culture for 24 h compared with uncultured cells. Expression of CYP2J3 and CYP2R1 either increased or did not change. It is concluded that CYP2C11 is a male-specific hepatic microsomal vitamin D 25-hydroxylase that hydroxylates vitamin D2, vitamin D3, 1{alpha}OHD2, and 1{alpha}OHD3. CYP2C11 is also a vitamin D 24-hydroxylase.

25-hydroxyvitamin D; 24-hydroxyvitamin D; liver microsomes; cytochrome P-450 enzymes


Address for reprint requests and other correspondence: N. H. Bell, Dept. of Medicine, Medical Univ. of South Carolina, Strom Thurmond Research Bldg., 114 Doughty St., PO Box 250775, Charleston, SC 29425 (E-mail: belln{at}musc.edu)






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