Cited by 1,933Vitamin D Research StudiesParathyroid Disorders and TreatmentsVitamin K Research Studies

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Vitamin D Metabolism, Mechanism of Action, and Clinical Applications

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Bikle, Daniel D.·2014·Chemistry & Biology

DOI 10.1016/j.chembiol.2013.12.016PMC PMC3968073

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Abstract

Vitamin D3 is made in the skin from 7-dehydrocholesterol under the influence of UV light. Vitamin D2 (ergocalciferol) is derived from the plant sterol ergosterol. Vitamin D is metabolized first to 25 hydroxyvitamin D (25OHD), then to the hormonal form 1,25-dihydroxyvitamin D (1,25(OH)2D). CYP2R1 is the most important 25-hydroxylase; CYP27B1 is the key 1-hydroxylase. Both 25OHD and 1,25(OH)2D are catabolized by CYP24A1. 1,25(OH)2D is the ligand for the vitamin D receptor (VDR), a transcription factor, binding to sites in the DNA called vitamin D response elements (VDREs). There are thousands of these binding sites regulating hundreds of genes in a cell-specific fashion. VDR-regulated transcription is dependent on comodulators, the profile of which is also cell specific. Analogs of 1,25(OH)2D are being developed to target specific diseases with minimal side effects. This review will examine these different aspects of vitamin D metabolism, mechanism of action, and clinical application.

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Authors: Bikle, D. D.
Affiliations: San Francisco VA Medical Center (US)
Corresponding author: Bikle, Daniel D.
ORCID: Bikle, Daniel D.
Venue: Chemistry & Biology
Publisher: Elsevier BV
Published: 2014-03
Volume: 21
Issue: 3
Pages: 319-329
ISSN: 1074-5521 (ISSN-L)
DOI: 10.1016/j.chembiol.2013.12.016
PMC: PMC3968073
OpenAlex: W1976776496
Cited by: 1,933
References: 133
Citations by year: 2026: 148 · 2025: 189 · 2024: 196 · 2023: 272 · 2022: 219 · 2021: 211 · 2020: 228 · 2019: 142 · 2018: 135 · 2017: 84 · 2016: 60 · 2015: 37 · 2014: 10
FWCI: 9.02
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 385 d)
Locations: Chemistry & Biology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: U.S. Department of Defense
National Institutes of Health (AR050023)
National Cancer Institute (CA110338)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR038386, R01AR050023, P01AR039448)
National Center for Research Resources (P41RR001614)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Vitamin D Research Studies
Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
Health Sciences › Nursing › Nutrition and Dietetics › Vitamin K Research Studies
Keywords: vitamin D metabolism, vitamin D3, vitamin D2, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, CYP2R1, CYP27B1, CYP24A1, vitamin D receptor, vitamin D response element, transcriptional regulation, vitamin D analogs, 7-dehydrocholesterol, ergosterol
MeSH terms: Cytochrome P-450 Enzyme System, DNA, Humans, Immune System, Metabolic Diseases, Neoplasms, Vitamin D, Receptors, Calcitriol, Response Elements

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