The CYP27B1 gene (CYP27B1 stands for: Cytochrome P450 Family 27 Subfamily B Member 1) is a protein-coding gene located on chromosome 12q14.1. An important paralog of this gene is CYP27A1.
CYP27B1 gene
DefinitionThis section has been translated automatically.
General informationThis section has been translated automatically.
The CYP27B1 gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and the synthesis of cholesterol, steroids and other lipids. The CYP27B1 protein is localized at the inner mitochondrial membrane, where it hydroxylates 25-hydroxyvitamin D3 at the 1alpha position. This reaction synthesizes 1alpha,25-dihydroxyvitamin D3, the active form of vitamin D3, which binds to the vitamin D receptor and regulates calcium metabolism. This enzyme thus regulates the level of biologically active vitamin D and plays an important role in calcium homeostasis.
PathophysiologyThis section has been translated automatically.
The CYP27B1 protein, cytochrome P450 monooxygenase, is involved in vitamin D metabolism and in calcium and phosphorus homeostasis. In the kidney, the enzyme catalyzes the hydroxylation of 25-hydroxyvitamin D3/calcidiol at the C1alpha position to form the hormonally active form of vitamin D3, 1alpha,25-dihydroxyvitamin D3/calcitriol, which acts via the vitamin D receptor (VDR). The oxygenase has 1alpha-hydroxylase activity on vitamin D intermediates of the CYP24A1-mediated inactivation pathway (Tang EKY et al. 2012). CYP27B1 oxygenase converts 24R,25-dihydroxyvitamin D3/secalciferol to 1-alpha,24,25-trihydroxyvitamin D3, an active ligand of VDR (vitamin D receptor). It is also active for 25-hydroxyvitamin D2 (Sawada N et al. 1999). Mechanistically, CYP27B1 utilizes molecular oxygen, which inserts one oxygen atom into a substrate and reduces the second to a water molecule, providing two electrons from NADPH via FDXR/adrenodoxin reductase and FDX1/adrenodoxin.
Clinical pictureThis section has been translated automatically.
Mutations in the CYP27B1 gene can lead to vitamin D-dependent rickets type I.
LiteratureThis section has been translated automatically.
- Sawada N et al. (1999) Enzymatic properties of human 25-hydroxyvitamin D3 1alpha-hydroxylase coexpression with adrenodoxin and NADPH-adrenodoxin reductase in Escherichia coli. Eur J Biochem 265:950-956.
- Tang EKY et al. (2012) Expression of human CYP27B1 in Escherichia coli and characterization in phospholipid vesicles. FEBS J 279:3749-3761.