[Recent studies on vitamin D metabolizing enzymes].
CYP27A1, CYP27B1, and CYP24A1 are members of the cytochrome P450 superfamily, and key enzymes of vitamin D(3) metabolism. CYP27A1 produced at least seven forms of minor metabolites including 1alpha, 25 (OH) (2)D(3) in addition to the major metabolite 25 (OH) D(3). In contrast, CYP27B1 appears to be a special enzyme to catalyze the hydroxylation at C-1alpha position of 25 (OH) D(3). Mutagenesis studies of CYP27B1 revealed the amino acid residues involved in substrate binding or interaction between CYP27B1 and adreno-doxin. On CYP24A1-dependent metabolism, remarkable metabolic processes of 1alpha, 25 (OH) (2)D(3) were observed. Rat CYP24A1 catalyzed six sequential monooxygenation reactions that convert 1alpha, 25 (OH) (2)D(3) into calcitroic acid. In addition to the C-24 oxidation pathway, human CYP24A1 catalyzed also C-23 oxidation pathway to produce 1alpha, 25 (OH) (2)D(3)-26, 23-lactone. Surprisingly, more than 70% of the vitamin D metabolites observed in a living body were found to be the products formed by the activities of CYP27A1, CYP27B1, and CYP24A1. In addition to the mitochondrial P450s, microsomal P450s also play important roles in vitamin D metabolism. Recent reports suggest that human microsomal CYP2R1 is more important than CYP27A1 as a vitamin D 25-hydroxylase. The decline in bone mineral density that occurs after long-term treatment with some antiepileptic drugs appears to be due to the increased 1alpha, 25 (OH) (2)D(3) metabolism by CYP3A4. Some vitamin D analogs are good substrates for CYP3A1 while CYP24A1 is responsible for metabolism of most of vitamin D analogs.
Sakaki
Toshiyuki
T
Toyama Prefectural University, Faculty of Engineering, Department of Biotechnology.
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D000818:Animals; D053493:Cholestanetriol 26-Monooxygenase; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000502:physiology*; D000072467:Cytochrome P450 Family 2; D006801:Humans; D009154:Mutation; D013250:Steroid Hydroxylases; D014807:Vitamin D / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase
D014807:Vitamin D; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase