Vitamin D Metabolism (Homo sapiens)

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VDR targets Hepatocyte Kidney Skin UV B radiation from sunlight Spontaneous isomerisation Endocrine modulators Vitamin D from Diet Vitamin D binding protein 7-Dehydro- cholesterol Previtamin D3 Cholecalciferol Calcidiol Calcidiol Inactive 24,25-OH- vitamin D Calcitriol CYP27B1 Parathyroid hormone CYP24A1 Vitamin D binding protein VDR alpha-globulin Cholesterol DHCR7 Ca Pi CYP2R1 CYP27A1 RXRA RXRB Activation Tissue-specific regulation Name: Vitamin D Metabolism License: CC BY 2.0 Organism: Homo sapiens


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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Ontology Terms

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Bibliography

  1. 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
  2. Waterham HR, Wanders RJ; ''Biochemical and genetic aspects of 7-dehydrocholesterol reductase and Smith-Lemli-Opitz syndrome.''; Biochim Biophys Acta, 2000 PubMed
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
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History

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RevisionActionTimeUserComment
96858view 16:32, 14 April 2018AlexanderPicoReverted to version '19:53, 15 September 2015' by AlexanderPico
96825view 17:37, 10 April 2018Artoria2e5Modified description
96824view 17:36, 10 April 2018Artoria2e5Modified description
82221view 19:53, 15 September 2015AlexanderPicofixing arrowheads for biopax conversion
74057view 03:23, 26 March 2014Mkutmonfixed unconnected lines, layout
73558view 15:18, 31 January 2014MaintBotremoves comments
71552view 12:26, 17 October 2013MaintBotUpdated data sources
70322view 03:11, 17 July 2013EveloModified title
70034view 18:59, 11 July 2013AlexanderPicoModified title
69840view 08:25, 11 July 2013EveloOntology Term : 'osteomalacia' added !
68004view 23:19, 28 June 2013EgonwMarked the VitD-binding protein as Protein (hoping that will fix the link to Uniprot/TrEMBL)
67745view 04:57, 26 June 2013DdiglesOntology Term : 'vitamin D metabolic pathway' added !
46487view 03:03, 2 February 2012LribeiroPeriodical save, work in progress
46379view 17:36, 23 January 2012KhanspersOntology Term : 'kidney cell' added !
46378view 17:35, 23 January 2012KhanspersOntology Term : 'hepatocyte' added !
46377view 17:35, 23 January 2012KhanspersOntology Term : 'skin fibroblast' added !
46376view 17:26, 23 January 2012KhanspersAdded xrefs, connected lines, changed graphical style
45011view 10:49, 6 October 2011KhanspersOntology Term : 'rickets' added !
45010view 10:45, 6 October 2011KhanspersOntology Term : 'metabolic pathway of cofactors and vitamins' added !
42790view 05:53, 30 April 2011LribeiroPeriodical save, work in progress
42789view 05:34, 30 April 2011LribeiroPeriodical save, work in progress
42788view 05:24, 30 April 2011LribeiroPeriodical save, work in progress
42787view 05:03, 30 April 2011LribeiroPeriodical save, work in progress
42786view 04:24, 30 April 2011LribeiroPeriodical save, work in progress
42785view 04:14, 30 April 2011LribeiroPeriodical save, work in progress
42784view 04:04, 30 April 2011LribeiroPeriodical save, work in progress
42778view 12:31, 29 April 2011LribeiroPeriodical save, work in progress
42777view 12:20, 29 April 2011LribeiroModified description
42776view 12:16, 29 April 2011LribeiroPeriodical save, work in progress
42775view 12:03, 29 April 2011LribeiroPeriodical save, work in progress
42774view 11:53, 29 April 2011LribeiroPeriodical save, work in progress
42773view 11:42, 29 April 2011LribeiroPeriodical save, work in progress
41192view 16:43, 1 March 2011MaintBotRemoved redundant pathway information and comments
38456view 11:18, 14 September 2010KhanspersChanged spacing and layout
38455view 11:17, 14 September 2010KhanspersPeriodical save, work in progress
38443view 15:26, 13 September 2010KhanspersUpdated xref for CYP2R1
38440view 02:37, 13 September 2010MartijnVanIerselTurned metabolites into circles
38425view 18:43, 10 September 2010AlexanderPicorearranged layout
38424view 16:19, 10 September 2010KhanspersMinor layout change
38423view 16:16, 10 September 2010Khanspersminor layout
38422view 15:58, 10 September 2010KhanspersAdded cell shapes, changed lines and datanode sizing
38421view 15:51, 10 September 2010KhanspersPeriodical save, work in progress
38420view 15:41, 10 September 2010KhanspersPeriodical save, work in progress
38419view 15:31, 10 September 2010KhanspersPeriodical save, work in progress
38418view 15:21, 10 September 2010KhanspersPeriodical save, work in progress
38328view 08:01, 1 September 2010EveloSpecify description
38327view 07:58, 1 September 2010EveloSpecify description
38326view 07:57, 1 September 2010EveloAdded target literature ref
38325view 07:48, 1 September 2010EveloPeriodical save, work in progress
38324view 07:37, 1 September 2010EveloModified description

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 D3MetaboliteHMDB06500 (HMDB)
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

<cite>No annotated interactions</cite>