Metabolism of 1alpha,25-dihydroxyvitamin D2 by human CYP24A1.
The metabolism of 1alpha,25-dihydroxyvitamin D2 (1alpha,25(OH)2D2) by human CYP24A1 was examined using the recombinant enzyme expressed in Escherichia coli cells. HPLC analysis revealed that human CYP24A1 produces at least 10 metabolites, while rat CYP24A1 produces only three metabolites, indicating a remarkable species-based difference in the CYP24A1-dependent metabolism of 1alpha,25(OH)2D2 between humans and rats. LC-MS analysis and periodate treatment of the metabolites strongly suggest that human CYP24A1 converts 1alpha,25(OH)2D2 to 1alpha,24,25,26(OH)4D2, 1alpha,24,25,28(OH)4D2, and 24-oxo-25,26,27-trinor-1alpha(OH)D2 via 1alpha,24,25(OH)3D2. These results indicate that human CYP24A1 catalyzes the C24-C25 bond cleavage of 1alpha,24,25(OH)2D2, which is quite effective in the inactivation of the active form of vitamin D2. The combination of hydroxylation at multiple sites and C-C bond cleavage could form a large number of metabolites. Our findings appear to be useful to predict the metabolism of vitamin D2 and its analogs in the human body.
Urushino
Naoko
N
Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
Yasuda
Kaori
K
Ikushiro
Shinichi
S
Kamakura
Masaki
M
Ohta
Miho
M
Sakaki
Toshiyuki
T
D053493:Cholestanetriol 26-Monooxygenase / Q000378:metabolism*; D006801:Humans; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism
C422824:1,25-dihydroxyvitamin D4; D014807:Vitamin D; D053493:Cholestanetriol 26-Monooxygenase