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Vitamin D (calciferol) metabolism
Stable Identifier
R-HSA-196791
DOI
10.3180/R-HSA-196791.4
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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Metabolism (Homo sapiens)
Metabolism of lipids (Homo sapiens)
Metabolism of steroids (Homo sapiens)
Vitamin D (calciferol) metabolism (Homo sapiens)
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Vitamin D3 (VD3, cholecalciferol) is a steroid hormone that principally plays roles in regulating intestinal calcium absorption and in bone metabolism. It is obtained from the diet and produced in the skin by photolysis of 7-dehydrocholesterol and released into the bloodstream. Very few foods (eg. oily fish, mushrooms exposed to sunlight and cod liver oil) are natural sources of vitamin D. A small number of countries in the world artificially fortify a few foods with vitamin D. The metabolites of vitamin D are carried in the circulation bound to a plasma protein called vitamin D binding protein (GC) (for review see Delanghe et al. 2015, Chun 2012). Vitamin D undergoes two subsequent hydroxylations to form the active form of the vitamin, 1-alpha, 25-dihydroxyvitamin D (1,25(OH)2D). The first hydroxylation takes place in the liver followed by subsequent transport to the kidney where the second hydroxylation takes place. 1,25(OH)2D acts by binding to nuclear vitamin D receptors (Neme et al. 2017) and it has been estimated that upwards of 2000 genes are directly or indirectly regulated which are involved in calcium homeostasis, immune responses, cellular growth, differentiation and apoptosis (Hossein-nezhad et al. 2013, Hossein-nezhad & Holick 2013). Inactivation of 1,25(OH)2D occurs via C23/C24 oxidation catalysed by cytochrome CYP24A1 enzyme (Christakos et al. 2016).
Literature References
PubMed ID
Title
Journal
Year
26681795
Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects
Carmeliet, G
,
Christakos, S
,
Dhawan, P
,
Verlinden, L
,
Verstuyf, A
Physiol. Rev.
2016
Participants
Events
Photolytic cleavage and thermal isomerization of 7-dehydroCHOL
(Homo sapiens)
VD3 translocates from ER membrane to extracellular region
(Homo sapiens)
VD3 binds GC
(Homo sapiens)
VD3 dissociates from GC
(Homo sapiens)
VD3 translocates from extracellular region to ER membrane
(Homo sapiens)
CYP2R1 25-hydroxylates VD3 to 25(OH)D
(Homo sapiens)
25(OH)D translocates from ER membrane to extracellular region
(Homo sapiens)
25(OH)D binds GC
(Homo sapiens)
CUBN binds GC:25(OH)D
(Homo sapiens)
LRP2-mediated uptake of extracellular CUBN:GC:25(OH)D
(Homo sapiens)
Endocytic translocation of CUBN:GC:25(OH)D to lysosomal lumen
(Homo sapiens)
LGMN degrades GC
(Homo sapiens)
CUBN dissociates from 25(OH)D
(Homo sapiens)
25(OH)D translocates from lysosomal lumen to cytosol
(Homo sapiens)
CYP27B1 hydroxylates 25(OH)D to 1,25(OH)2D
(Homo sapiens)
CYP24A1 hydroxylates 1,25(OH)2D, inactivating it
(Homo sapiens)
1,25(OH)2D translocates from cytosol to nucleoplasm
(Homo sapiens)
1,25(OH)2D binds VDR
(Homo sapiens)
PIAS4 SUMOylates VDR with SUMO2
(Homo sapiens)
VDR agonists bind VDR
(Homo sapiens)
Participates
as an event of
Metabolism of steroids (Homo sapiens)
Event Information
Go Biological Process
vitamin D metabolic process (0042359)
Orthologous Events
Vitamin D (calciferol) metabolism (Bos taurus)
Vitamin D (calciferol) metabolism (Caenorhabditis elegans)
Vitamin D (calciferol) metabolism (Canis familiaris)
Vitamin D (calciferol) metabolism (Danio rerio)
Vitamin D (calciferol) metabolism (Dictyostelium discoideum)
Vitamin D (calciferol) metabolism (Drosophila melanogaster)
Vitamin D (calciferol) metabolism (Gallus gallus)
Vitamin D (calciferol) metabolism (Mus musculus)
Vitamin D (calciferol) metabolism (Rattus norvegicus)
Vitamin D (calciferol) metabolism (Sus scrofa)
Vitamin D (calciferol) metabolism (Xenopus tropicalis)
Authored
Jassal, B (2008-10-01)
Reviewed
D'Eustachio, P (2008-05-28)
Created
Jassal, B (2007-04-24)
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