Vitamin D metabolism (Homo sapiens)

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2VDR targets4Endocrine modulatorsUV B radiation from sunlightTissue-specific regulationVitamin D from DietHepatocyteActivationKidneySpontaneous isomerisationCYP27A1CYP27B11alpha-hydroxylaseCYP2R1 Previtamin D3RXRAPi7-DehydrocholesterolRXRBCalcidiol25-Hydroxyvitamin D3CholecalciferolVitamin D3Inactive 24,25-Dihydroxyvitamin Dalpha-globulinCalcitriolActive 1,25-Dihydroxyvitamin DVDRVitamin D binding proteinCYP24A124-hydroxylaseCaVitamin D binding proteinParathyroid hormoneCalcidiol25-Hydroxyvitamin D331


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. 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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History

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CompareRevisionActionTimeUserComment
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
128572view13:59, 13 February 2024EweitzRefine cell label graphics to mitigate site rendering bug
128571view13:54, 13 February 2024EweitzEconomize layout
128570view13:19, 13 February 2024EweitzEconomize layout
128569view04:57, 13 February 2024EweitzStandardize font, economize layout, refine legend, standardize case
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
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

External references

DataNodes

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NameTypeDatabase referenceComment
7-DehydrocholesterolMetaboliteHMDB00032 (HMDB)
CYP24A1 24-hydroxylaseGeneProduct1591 (Entrez Gene)
CYP27A1GeneProduct1593 (Entrez Gene)
CYP27B1 1alpha-hydroxylaseGeneProduct1594 (Entrez Gene)
CYP2R1 GeneProduct1593 (Entrez Gene)
CaMetaboliteHMDB00464 (HMDB)
Calcidiol 25-Hydroxyvitamin D3MetaboliteHMDB03550
Calcidiol 25-Hydroxyvitamin D3MetaboliteHMDB03550 (HMDB)
Calcitriol Active 1,25-Dihydroxyvitamin DMetaboliteHMDB01903 (HMDB)
Cholecalciferol Vitamin D3MetaboliteHMDB00876 (HMDB)
Inactive 24,25-Dihydroxyvitamin DMetaboliteHMDB00430 (HMDB)
Parathyroid hormoneGeneProductP01270 (Uniprot/TrEMBL)
PiMetaboliteHMDB01429 (HMDB)
Previtamin D3MetaboliteHMDB06500 (HMDB)
RXRAGeneProduct6256 (Entrez Gene)
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RXRBGeneProduct6257
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VDRGeneProduct7421 (Entrez Gene)
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Vitamin D binding proteinGeneProductP02774 (Uniprot/TrEMBL)
alpha-globulinGeneProduct

Annotated Interactions

No annotated interactions

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