Vitamin D Metabolism (Homo sapiens)

From WikiPathways

Jump to: navigation, search


Curation Tags

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).

Ontology Tags

 

Bibliography

View all...
  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

History

View all...
CompareRevisionActionTimeUserComment
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
70034view01:59, 12 July 2013AlexanderPicoModified title
69840view15:25, 11 July 2013EveloOntology Term : 'osteomalacia' added !
68004view06:19, 29 June 2013EgonwMarked the VitD-binding protein as Protein (hoping that will fix the link to Uniprot/TrEMBL)
67745view11:57, 26 June 2013DdiglesOntology Term : 'vitamin D metabolic pathway' added !
46487view10:03, 2 February 2012LribeiroPeriodical save, work in progress
46379view00:36, 24 January 2012KhanspersOntology Term : 'kidney cell' added !
46378view00:35, 24 January 2012KhanspersOntology Term : 'hepatocyte' added !
46377view00:35, 24 January 2012KhanspersOntology Term : 'skin fibroblast' added !
46376view00:26, 24 January 2012KhanspersAdded xrefs, connected lines, changed graphical style
45011view17:49, 6 October 2011KhanspersOntology Term : 'rickets' added !
45010view17:45, 6 October 2011KhanspersOntology Term : 'metabolic pathway of cofactors and vitamins' added !
42790view12:53, 30 April 2011LribeiroPeriodical save, work in progress
42789view12:34, 30 April 2011LribeiroPeriodical save, work in progress
42788view12:24, 30 April 2011LribeiroPeriodical save, work in progress
42787view12:03, 30 April 2011LribeiroPeriodical save, work in progress
42786view11:24, 30 April 2011LribeiroPeriodical save, work in progress
42785view11:14, 30 April 2011LribeiroPeriodical save, work in progress
42784view11:04, 30 April 2011LribeiroPeriodical save, work in progress
42778view19:31, 29 April 2011LribeiroPeriodical save, work in progress
42777view19:20, 29 April 2011LribeiroModified description
42776view19:16, 29 April 2011LribeiroPeriodical save, work in progress
42775view19:03, 29 April 2011LribeiroPeriodical save, work in progress
42774view18:53, 29 April 2011LribeiroPeriodical save, work in progress
42773view18:42, 29 April 2011LribeiroPeriodical save, work in progress
41192view23:43, 1 March 2011MaintBotRemoved redundant pathway information and comments
38456view18:18, 14 September 2010KhanspersChanged spacing and layout
38455view18:17, 14 September 2010KhanspersPeriodical save, work in progress
38443view22:26, 13 September 2010KhanspersUpdated xref for CYP2R1
38440view09:37, 13 September 2010MartijnVanIerselTurned metabolites into circles
38425view01:43, 11 September 2010AlexanderPicorearranged layout
38424view23:19, 10 September 2010KhanspersMinor layout change
38423view23:16, 10 September 2010Khanspersminor layout
38422view22:58, 10 September 2010KhanspersAdded cell shapes, changed lines and datanode sizing
38421view22:51, 10 September 2010KhanspersPeriodical save, work in progress
38420view22:41, 10 September 2010KhanspersPeriodical save, work in progress
38419view22:31, 10 September 2010KhanspersPeriodical save, work in progress
38418view22:21, 10 September 2010KhanspersPeriodical save, work in progress
38328view15:01, 1 September 2010EveloSpecify description
38327view14:58, 1 September 2010EveloSpecify description
38326view14:57, 1 September 2010EveloAdded target literature ref
38325view14:48, 1 September 2010EveloPeriodical save, work in progress
38324view14:37, 1 September 2010EveloModified description
38296view15:09, 30 August 2010LribeiroPeriodical save, work in progress
38295view14:36, 30 August 2010EveloAdded RXRB, and illustrated complex formation
38294view14:26, 30 August 2010EveloCorrected VDR, added RXRA
37526view14:51, 8 June 2010LribeiroModified description

External references

View all...
NameTypeDatabase referenceComment
CYP27A1GeneProduct1593 (Entrez Gene)
Previtamin D3MetaboliteHMDB06500 (HMDB)
CaMetaboliteHMDB00464 (HMDB)
CholecalciferolMetaboliteHMDB00876 (HMDB)
CholesterolMetaboliteHMDB00067 (HMDB)
CalcidiolMetaboliteHMDB03550 (HMDB)
VDRGeneProduct7421 (Entrez Gene)
CYP2R1 GeneProduct120227 (Entrez Gene)
RXRBGeneProduct6257 (Entrez Gene)
Inactive

24,25-OH-

vitamin D
MetaboliteHMDB00430 (HMDB)
7-Dehydro- cholesterolMetaboliteHMDB00032 (HMDB)
CalcitriolMetaboliteHMDB01903 (HMDB)
PiMetaboliteHMDB01429 (HMDB)
CYP27B1GeneProduct1594 (Entrez Gene)
Vitamin D binding proteinProteinP02774 (Uniprot-TrEMBL)
Parathyroid hormoneGeneProduct5741 (Entrez Gene)
RXRAGeneProduct6256 (Entrez Gene)
CYP24A1GeneProduct1591 (Entrez Gene)
alpha-globulinGeneProduct
Vitamin D binding proteinGeneProduct2638 (Entrez Gene)
DHCR7GeneProduct1717 (Entrez Gene)
Personal tools
Navigation