Non-classical role of vitamin D (Homo sapiens)

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1HTN & CVDSkinKidneySARS Cov-2 with genomeIncrease in Na, K retention, Increase vasoconstrictionBlood streamDiabetesSARS glycoprotein spike& anti-proliferationUV (295-320 nm)LiverStrongImmunity3Cholecalciferol1-alpha-hydroxylase ACE2VasodilationRenal Type-1 angiotensin II receptorACEType-2 angiotensin II receptor7-Dehydrocholesterol25-hydroxylasealdosterone1,25-dihydroxycholecalciferol1,25-dihydroxycholecalciferolcytokines and inflammationAngiotensin IIAngiotensinogenApoptosisInflammationType-1 angiotensin II receptorvitamin D receptor agonistsFibrosisangiotensin I25-hydroxycholecalciferolROS productionReninS42S


Vitamin D is known for its participation in various skeletal and non-skeletal muscle homeostasis. In addition to Calcium (Ca²⁺) and phosphorous (P) absorption, its association with CVD, hypertention, cancer, obesity, diabetes and immune system has been reported. It actively participates in the regulation of cardiovascular system through Renin Angiotensin Aldosterone System (RAAS). Renin is secreted by the kidney and it activates the formation of angiotensin II that leads to the decreased production of nitric oxide (NO) and increased endothelial vascular dysfunction (Pérez-Hernández et al., 2016). Vitamin D causes the insulin release, facilitates muscle contraction and glucose uptake by enhancing the activity of glucose transporter 4 (GLUT4) channels in the cells (Berridge, 2017) and reduces the aldosterone . From last few years vitamin D has gained special attention as immunomodulatory agent. The immunologic cells such as B cells, T cells, and antigen presenting cells express vitamin D receptors on their cells as well as are capable of synthesizing vitamin D metabolites especially calcitriol. The beneficial effects of vitamin D are linked with both innate and adaptive immune systems. During vitamin D deficiency an unwanted production of pro-inflammatory cytokines cause atherosclerotic lesions and atherogenesis. These conditions lead to increased vasoconstriction and decreased vasodilation, endothelial dysfunction, and alleviated nitric oxide formation. Furthermore, the expression of angiotensin-converting enzyme 2 (ACE2; responsible for the retrospective production of Ang1-7 form Ang II) is also reduced in vitamin D deficient subjects. Such individuals are more vulnerable to infectious diseases, especially, recent pandemic of COVID-19 (Malek Mahdavi, 2020).

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  1. Malek Mahdavi A; ''A brief review of interplay between vitamin D and angiotensin-converting enzyme 2: Implications for a potential treatment for COVID-19.''; Rev Med Virol, 2020 PubMed Europe PMC Scholia
  2. Berridge MJ; ''Vitamin D deficiency and diabetes.''; Biochem J, 2017 PubMed Europe PMC Scholia
  3. McLachlan CS; ''The angiotensin-converting enzyme 2 (ACE2) receptor in the prevention and treatment of COVID-19 are distinctly different paradigms.''; Clin Hypertens, 2020 PubMed Europe PMC Scholia
  4. Pérez-Hernández N, Aptilon-Duque G, Nostroza-Hernández MC, Vargas-Alarcón G, Rodríguez-Pérez JM, Blachman-Braun R; ''Vitamin D and its effects on cardiovascular diseases: a comprehensive review.''; Korean J Intern Med, 2016 PubMed Europe PMC Scholia


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124643view12:59, 18 November 2022NhungPAdjust layout to improve readability
121511view03:29, 20 February 2022EweitzModified title
120956view10:17, 3 February 2022EgonwModified description
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120233view11:29, 17 November 2021EweitzModified title
120115view14:02, 4 November 2021HumeraFiazChanges in references
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120113view13:54, 4 November 2021HumeraFiazUpdated some graphical elements and added bibliography.
120105view15:11, 3 November 2021HumeraFiazModified description
120104view15:07, 3 November 2021HumeraFiazOntology Term : 'diabetes mellitus' added !
120103view14:51, 3 November 2021HumeraFiazModified description
120095view12:12, 2 November 2021SusanOntology Term : 'hypertension' added !
119959view10:56, 30 September 2021SusanOntology Term : 'COVID-19' added !
119958view10:55, 30 September 2021SusanOntology Term : 'vitamin D signaling pathway' added !
119957view10:55, 30 September 2021SusanOntology Term : 'vitamin D metabolic pathway' added !
119949view17:31, 28 September 2021HumeraFiazNew pathway

External references


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NameTypeDatabase referenceComment
1,25-dihydroxycholecalciferolMetaboliteCHEBI:17823 (ChEBI)
1-alpha- hydroxylase ProteinV9GYP0 (Uniprot-TrEMBL)
25-hydroxycholecalciferolMetaboliteCHEBI:17933 (ChEBI)
25-hydroxylaseProteinE9PS56 (Uniprot-TrEMBL)
7-DehydrocholesterolMetaboliteCHEBI:17759 (ChEBI)
ACE2ProteinQ9BYF1 (Uniprot-TrEMBL)
ACEProteinA0A0A0MSN4 (Uniprot-TrEMBL)
Angiotensin IIMetaboliteHMDB01035 (HMDB)
AngiotensinogenProteinP01019 (Uniprot-TrEMBL)
ApoptosisPathwayWP254 (WikiPathways)
CholecalciferolMetaboliteCHEBI:28940 (ChEBI)
FibrosisPathwayWP3624 (WikiPathways)
InflammationPathwayWP4479 (WikiPathways)
ROS productionPathwayWP4969 (WikiPathways)
Renal Type-1

angiotensin II

ProteinP30556 (Uniprot-TrEMBL)
ReninProteinP00797 (Uniprot-TrEMBL)

angiotensin II

ProteinP30556 (Uniprot-TrEMBL)

angiotensin II

ProteinP50052 (Uniprot-TrEMBL)
VasodilationPathwayWP4580 (WikiPathways)
aldosteroneMetaboliteQ184564 (Wikidata)
angiotensin IMetaboliteCHEBI:2718 (ChEBI)
cytokines and inflammationPathwayWP530 (WikiPathways)
vitamin D receptor agonistsMetaboliteCHEBI:139503 (ChEBI)

Annotated Interactions

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