Vitamin D synthesis (Homo sapiens)
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Photochemical synthesis of vitamin D3 (cholecalciferol, D3) occurs cutaneously where pro-vitamin D3 (7-dehydrocholesterol) is converted to pre-vitamin D3 (pre-D3) in response to ultraviolet B (sunlight) exposure. DHCR7 encodes the enzyme 7-dehydrocholesterol (7-DHC) reductase, which converts 7-DHC to cholesterol, thereby removing the substrate from the synthetic pathway of vitamin D3, a precursor of 25-hydroxyvitamin D3.The finding that common variants at DHCR7 are strongly associated with circulating 25-hydroxyvitamin D concentrations suggests that this enzyme could have a larger role in regulation of vitamin D status than has previously been recognised. Vitamin D3, obtained from the isomerization of pre-vitamin D3 in the epidermal basal layers or intestinal absorption of natural and fortified foods and supplements, binds to vitamin D-binding protein (DBP) in the bloodstream, and is transported to the liver. D3 is hydroxylated by liver 25-hydroxylases (25-OHase). The resultant 25-hydroxycholecalciferol (25(OH)D3) is 1-hydroxylated in the kidney by 25-hydroxyvitamin D3-1 -hydroxylase (1-OHase). This yields the active secosteroid 1 ,25(OH)2D3 (calcitriol), which has different effects on various target tissues. The synthesis of 1,25(OH)2D3 from 25(OH)D3 is stimulated by parathyroid hormone (PTH) and suppressed by Ca2+, Pi and 1,25(OH)2D3 itself. The rate-limiting step in catabolism is the degradation of 25(OH)D3 and 1,25(OH)2D3 to 24,25(OH)D3 and 1,24,25(OH)2D3, respectively,which occurs through 24-hydroxylation by 25-hydroxyvitamin D 24-hydroxylase (24-OHase), encoded by the CYP24A1 gene. 24,25(OH)D3 and 1,24,25(OH)2D3 are consequently excreted. Vitamin D activity is mediated through binding of 1,25(OH)2D3 to the vitamin D receptor (VDR), which can regulate transcription of other genes involved in cell regulation, growth, and immunity. VDR modulates the expression of genes by forming a heterodimer complex with retinoid-X-receptors (RXR).
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- Guo YD, Strugnell S, Back DW, Jones G; ''Transfected human liver cytochrome P-450 hydroxylates vitamin D analogs at different side-chain positions.; ''Proc Natl Acad Sci U S A, 1993 - PubMed
- Ahn J, Yu K, Stolzenberg-Solomon R, Simon KC, McCullough ML, Gallicchio L, Jacobs EJ, Ascherio A, Helzlsouer K, Jacobs KB, Li Q, Weinstein SJ, Purdue M, Virtamo J, Horst R, Wheeler W, Chanock S, Hunter DJ, Hayes RB, Kraft P, Albanes D; ''Genome-wide association study of circulating vitamin D levels.; ''Hum Mol Genet. 2010 Jul 1;19(13):2739-45, 2010 - PubMed
- Cheng JB, Levine MA, Bell NH, Mangelsdorf DJ, Russell DW; ''Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase.; ''Proc Natl Acad Sci U S A, 2004 - PubMed
- Waterham HR, Wanders RJ; ''Biochemical and genetic aspects of 7-dehydrocholesterol reductase and Smith-Lemli-Opitz syndrome; ''Biochim Biophys Acta. 2000 Dec 15;1529(1-3):340-56, 2000 - PubMed
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External references
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| Name | Type | Database reference |
|---|---|---|
| CYP27A1 | GeneProduct | 1593 (Entrez Gene)  |
| Previtamin D3 | Metabolite | HMDB06500 (HMDB) |
| Ca | Metabolite | HMDB00464 (HMDB) |
| Cholecalciferol | Metabolite | HMDB00876 (HMDB) |
| Cholesterol | Metabolite | HMDB00067 (HMDB) |
