Vitamin D metabolism (Homo sapiens)

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6VDR targets Skin5Vitamin D from DietUV B radiation from sunlightEndocrine modulatorsSpontaneous isomerisationLegend:CholecalciferolVDRPrevitamin D3CYP27A1RXRB7-Dehydro-cholesterolDHCR7CalcitriolCalcidiolCYP2R1 CYP24A1Vitamin D binding proteinPialpha-globulinInactive24,25-OH-vitamin DCholesterolCaCalcidiolParathyroid hormoneRXRAVitamin D binding proteinCYP27B11, 4, 82Activation3Tissue-specific regulationHepatocyteKidney


Description

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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Bibliography

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  1. 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 Europe PMC Scholia
  2. Thomas J Wang*, Feng Zhang*, J Brent Richards*, Bryan Kestenbaum*, Joyce B van Meurs*, Diane Berry*, Douglas P Kiel, Elizabeth A Streeten, Claes Ohlsson, Daniel L Koller, Leena Peltonen†, Jason D Cooper, Paul F O’Reilly, Denise K Houston, Nicole L Glazer, Liesbeth Vandenput, Munro Peacock, Julia Shi, Fernando Rivadeneira, Mark I McCarthy, Pouta Anneli, Ian H de Boer, Massimo Mangino, Bernet Kato, Deborah J Smyth, Sarah L Booth, Paul F Jacques, Greg L Burke, Mark Goodarzi, Ching-Lung Cheung, Myles Wolf, Kenneth Rice, David Goltzman, Nick Hidiroglou, Martin Ladouceur, Nicholas J Wareham, Lynne J Hocking, Deborah Hart, Nigel K Arden, Cyrus Cooper, Suneil Malik, William D Fraser, Anna-Liisa Hartikainen, Guangju Zhai, Helen M Macdonald, Nita G Forouhi, Ruth J F Loos, David M Reid, Alan Hakim, Elaine Dennison, Yongmei Liu, Chris Power, Helen E Stevens, Laitinen Jaana, Ramachandran S Vasan, Nicole Soranzo, Jörg Bojunga, Bruce M Psaty, Mattias Lorentzon, Tatiana Foroud, Tamara B Harris, Albert Hofman, John-Olov Jansson, Jane A Cauley, Andre G Uitterlinden, Quince Gibson, Marjo-Riitta Järvelin, David Karasik, David S Siscovick, Michael J Econs, Stephen B Kritchevsky, Jose C Florez, John A Todd*, Josee Dupuis*, Elina Hyppönen*, Timothy D Spector*; ''Common genetic determinants of vitamin D insufficiency: a genome-wide association study''; Lancet,376:180-188, 2010 PubMed Europe PMC Scholia
  3. Ramagopalan SV, Heger A, Berlanga AJ, Maugeri NJ, Lincoln MR, Burrell A, Handunnetthi L, Handel AE, Disanto G, Orton SM, Watson CT, Morahan JM, Giovannoni G, Ponting CP, Ebers GC, Knight JC; ''A ChIP-seq defined genome-wide map of vitamin D receptor binding: Associations with disease and evolution.''; Genome Res, 2010 PubMed Europe PMC Scholia
  4. Norman AW; ''From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health.''; Am J Clin Nutr, 2008 PubMed Europe PMC Scholia
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  6. 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 Europe PMC Scholia
  7. Waterham HR, Wanders RJ; ''Biochemical and genetic aspects of 7-dehydrocholesterol reductase and Smith-Lemli-Opitz syndrome.''; Biochim Biophys Acta, 2000 PubMed Europe PMC Scholia

History

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142319view13:30, 1 January 2026EgonwMore removed newlines
142298view15:24, 30 December 2025EgonwRemove the newlines in the author list
142297view15:23, 30 December 2025EgonwFixed a Wikidata identifier
142296view15:22, 30 December 2025Egonwmim-translocation
137603view17:55, 5 March 2025KhanspersModified description
136604view02:43, 14 February 2025EweitzRefine interaction alignment
136603view02:42, 14 February 2025EweitzEconomize layout
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136584view02:07, 14 February 2025EweitzOrder cell membranes to back z-index layer
136583view02:05, 14 February 2025EweitzUse prior topology, per meeting feedback
128578view04:31, 14 February 2024EweitzFix site-PathVisio discrepancy in text width, distinguish process via color, use gene symbol
128573view14:00, 13 February 2024EweitzRefine metabolite placement
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118354view13:32, 27 May 2021Mkutmonfix publication ref
117856view15:20, 22 May 2021EweitzModified title
107120view14:19, 17 September 2019MaintBotChEBI identifier normalization
106185view12:08, 16 August 2019MaintBotHMDB identifier normalization
105853view23:17, 15 August 2019KhanspersModified description
104243view15:25, 11 May 2019EgonwRemoved the RHEA: prefix from the identifier.
103420view09:22, 28 February 2019DeSlAdded rhea to reaction from 7-DH-cholesterol to cholesterol+MIM-modification to MIM-conversion; changed ID for previtamin D3 from HMDb to ChEBI; changed MIMconversion to MImmodification for reaction with sunlight.
101956view09:20, 21 November 2018DeSlChanged layout for readability.
101955view09:08, 21 November 2018DeSlRemoved licence number
96858view23:32, 14 April 2018AlexanderPicoReverted to version '19:53, 15 September 2015' by AlexanderPico
96825view00:37, 11 April 2018Artoria2e5Modified description
96824view00:36, 11 April 2018Artoria2e5Modified description
82221view02:53, 16 September 2015AlexanderPicofixing arrowheads for biopax conversion
74057view10:23, 26 March 2014Mkutmonfixed unconnected lines, layout
73558view22:18, 31 January 2014MaintBotremoves comments
71552view19:26, 17 October 2013MaintBotUpdated data sources
70322view10:11, 17 July 2013EveloModified title

External references

DataNodes

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NameTypeDatabase referenceComment
7-Dehydro- cholesterolMetaboliteHMDB00032 (HMDB)
CYP24A1GeneProduct1591 (Entrez Gene)
CYP27A1GeneProduct1593 (Entrez Gene)
CYP27B1GeneProduct1594 (Entrez Gene)
CYP2R1 GeneProduct120227 (Entrez Gene)
CaMetaboliteHMDB00464 (HMDB)
CalcidiolMetaboliteHMDB03550 (HMDB)
CalcitriolMetaboliteHMDB01903 (HMDB)
CholecalciferolMetaboliteHMDB00876 (HMDB)
CholesterolMetaboliteHMDB00067 (HMDB)
DHCR7GeneProduct1717 (Entrez Gene)
Inactive

24,25-OH-

vitamin D		MetaboliteHMDB00430 (HMDB)
Parathyroid hormoneGeneProduct5741 (Entrez Gene)
PiMetaboliteHMDB01429 (HMDB)
Previtamin D3Metabolite8403 (ChEBI)
RXRAGeneProduct6256 (Entrez Gene)
RXRBGeneProduct6257 (Entrez Gene)
VDRGeneProduct7421 (Entrez Gene)
Vitamin D binding proteinGeneProduct2638 (Entrez Gene)
Vitamin D binding proteinProteinP02774 (Uniprot-TrEMBL)
alpha-globulinGeneProduct

Annotated Interactions

SourceTargetTypeDatabase referenceComment
7-Dehydro- cholesterolCholesterolmim-conversion23986 (Rhea)
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