Vitamin D Metabolism (Bos taurus)

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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).

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP1531(74057) with a 91.0% conversion rate.

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Bibliography

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

History

CompareRevisionActionTimeUserComment
80731view15:23, 30 June 2015MkutmonNew pathway

External references

Datanodes

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NameTypeDatabase referenceComment
7-Dehydro- cholesterolMetaboliteHMDB00032 (HMDB)
CYP24A1GeneProductENSBTAG00000002765 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1591
CYP27A1GeneProductENSBTAG00000013489 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1593
CYP27B1GeneProductENSBTAG00000016906 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1594
CYP2R1GeneProductENSBTAG00000010419 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:120227
CaMetaboliteHMDB00464 (HMDB)
CalcidiolMetaboliteHMDB03550 (HMDB)
CalcitriolMetaboliteHMDB01903 (HMDB)
CholecalciferolMetaboliteHMDB00876 (HMDB)
CholesterolMetaboliteHMDB00067 (HMDB)
DHCR7GeneProductENSBTAG00000016465 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1717
GCProteinENSBTAG00000013718 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P02774
Inactive

24,25-OH-

vitamin D
MetaboliteHMDB00430 (HMDB)
PTHGeneProductENSBTAG00000019080 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5741
PiMetaboliteHMDB01429 (HMDB)
Previtamin D3MetaboliteHMDB06500 (HMDB)
RXRAGeneProductENSBTAG00000017851 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6256
RXRBGeneProductENSBTAG00000000602 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6257
VDRGeneProductENSBTAG00000016414 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7421
alpha-globulinGeneProduct

Annotated Interactions

No annotated interactions
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