The DOI matches its Crossref record; 131 of the 133 references it cites were found in a registry or an index.
Vitamin D Metabolism, Mechanism of Action, and Clinical Applications
Open accessAbstract
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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“Vitamin D3 is modified through the mitochondria in the liver and kidney to assume its active form, 1,25 vitamin D (Bikle, 2014).”
From Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact (2020) · cites this paper as Bikle, 2014
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“supplementation effects depend strongly on baseline status, assay standardization, dose, formulation, adherence, and population context [1,2,3,4,5,6].”
From Vitamin D Supplementation, Total Testosterone, and Androgen Bioavailability Markers in Adult Men: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (2026) · cites this paper as [2]
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“Many other tissues express CYP27B1 too which can modulate the local level of this hormone utilizing plasma 25(OH)D as substrate [10, 14, 51].”
From The serum vitamin D metabolome: what we know and what is still to discover (2019) · cites this paper as [14]
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“Serum 1α,25(OH)2D3 and 1α,25(OH)2D2 are produced in the kidney by the action of CYP27B1 on 25(OH)D obtained from the circulation [14].”
From The serum vitamin D metabolome: what we know and what is still to discover (2019) · cites this paper as [14]
In the citing paper
“3-Epi-1α,25(OH)2D3 generally has reduced biological activity compared to 1α,25(OH)2D3 [14, 73–75] and is discussed further in Sections 2.1.3 and 3.6.”
From The serum vitamin D metabolome: what we know and what is still to discover (2019) · cites this paper as [14]
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Cites
1 retracted
RETRACTED: 1α,25(OH)2D3-induced DNA methylation suppresses the human CYP27B1 gene
Kim, M. S., Fujiki, R., Kitagawa, H., & Kato, S. (2007) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2006.12.014 · Cited by 83
RetractedToll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response
Liu, P. T., Stenger, S., Li, H., Wenzel, L., Tan, B. H., Krutzik, S. R., Ochoa, M. T., Schauber, J., Wu, K., Meinken, C., et al. (2006) · Science · doi:10.1126/science.1123933 · Cited by 3,924
Mapping and analysis of chromatin state dynamics in nine human cell types
Ernst, J., Kheradpour, P., Mikkelsen, T. S., Shoresh, N., Ward, L. D., Epstein, C. B., Zhang, X., Wang, L., Issner, R., Coyne, M., et al. (2011) · Nature · doi:10.1038/nature09906 · Cited by 2,898
The Role of Vitamin D and Calcium in Type 2 Diabetes. A Systematic Review and Meta-Analysis
Pittas, A. G., Lau, J., Hu, F. B., & Dawson-Hughes, B. F. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-0298 · Cited by 2,048
Klotho converts canonical FGF receptor into a specific receptor for FGF23
Urakawa, I., Yamazaki, Y., Shimada, T., Iijima, K., Hasegawa, H., Okawa, K., Fujita, T., Fukumoto, S., & Yamashita, T. (2006) · Nature · doi:10.1038/nature05315 · Cited by 1,865
Gombart, A. F., Borregaard, N., & Koeffler, H. P. (2005) · The FASEB Journal · doi:10.1096/fj.04-3284com · Cited by 1,145
Immunoregulation by 1,25-dihydroxyvitamin D3: Basic concepts
van Etten, E., & Mathieu, C. (2005) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2005.06.002 · Cited by 882
Ramagopalan, S. V., Heger, A., Berlanga‐Taylor, A. J., Maugeri, N., Lincoln, M. R., Burrell, A., Handunnetthi, L., Handel, A. E., Disanto, G., Orton, S. M., et al. (2010) · Genome Research · doi:10.1101/gr.107920.110 · Cited by 881
The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand
Rochel, N., Wurtz, J. M., Mitschler, A., Klaholz, B., & Moras, D. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80413-x · Cited by 842
Tripkovic, L., Lambert, H., Hart, K. H., Smith, C. P. S., Bucca, G., Penson, S., Chope, G. A., Hyppönen, E., Berry, J., Vieth, R., et al. (2012) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.111.031070 · Cited by 786
Research works printed but not linked: 1
- Norman, 1997, Mol. Endocrinol., 11, 1518
Cited by
Sorted by citations
Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects
Christakos, S., Dhawan, P., Verstuyf, A., Verlinden, L., & Carmeliet, G. (2015) · Physiological Reviews · doi:10.1152/physrev.00014.2015 · Cited by 2,105
Exploring vitamin D metabolism and function in cancer
Jeon, S., & Shin, E. (2018) · Experimental & Molecular Medicine · doi:10.1038/s12276-018-0038-9 · Cited by 581
Roth, D. E., Abrams, S. A., Aloia, J. F., Bergeron, G., Bourassa, M. W., Brown, K. H., Calvo, M. S., Cashman, K. D., Combs, G. F., De‐Regil, L. M., et al. (2018) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13968 · Cited by 541
How UV Light Touches the Brain and Endocrine System Through Skin, and Why
Slominski, A. T., Zmijewski, M. A., Plonka, P. M., Szaflarski, J. P., & Paus, R. (2018) · Endocrinology · doi:10.1210/en.2017-03230 · Cited by 452
Vitamin D Toxicity–A Clinical Perspective
Marcinowska-Suchowierska, E., Kupisz-Urbańska, M., Łukaszkiewicz, J., Płudowski, P., & Jones, G. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00550 · Cited by 447
Metadata
- 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)
- 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
- 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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