Vitamin D3 (25-OH-Cholecalciferol): the pathway in the body

Vitamin D3 (25-OH-Cholecalciferol) is part of the pathway “Vitamin D”. This page shows the whole pathway; the station of Vitamin D3 (25-OH-Cholecalciferol) is highlighted.

Where this laboratory value sits: 25-OH-vitamin D3 — calcidiol, form in blood. In the liver, mainly the enzyme CYP2R1 attaches an OH group. This forms calcidiol, the form that circulates in the blood bound to vitamin D-binding protein. Source 1, 4

In brief

Vitamin D is a fat-soluble hormone precursor formed in the skin under UVB light or taken in with food. The liver and kidney convert it into calcitriol, which controls the reading of certain genes in the cell nucleus.

The pathway step by step

1. 7-Dehydrocholesterol → Previtamin D3 · UVB light UVB light breaks open one ring of the molecule. This forms previtamin D3, a purely light-driven step that involves no enzyme. Source 3
2. Previtamin D3 → Vitamin D3 · Body heat The warmth of the skin rearranges previtamin D3 into vitamin D3. Vitamin D from food reaches the same point in the pathway via the gut. Source 3, 1
3. Vitamin D3 → 25-OH-vitamin D3 CYP2R1 (liver) · NADPH In the liver, mainly the enzyme CYP2R1 attaches an OH group. This forms calcidiol, the form that circulates in the blood bound to vitamin D-binding protein. Source 1, 4
4. Calcitriol → VDR in the nucleus · VDR and RXR Calcitriol binds to the vitamin D receptor. Together with its partner RXR, the receptor attaches to specific sections of DNA. Source 2
5. VDR in the nucleus → Target genes The receptor pair switches the reading of certain genes on or off. These include genes for calcium transport, bone remodelling and immune cells. Source 2
6. Target genes → Calcium transport TRPV6, calbindin Two of these gene products are the channel TRPV6 and the transport protein calbindin. They move calcium from the gut into the cell and on into the blood. Source 2
7. Calcitriol → Calcitroic acid CYP24A1 · NADPH The enzyme CYP24A1 breaks down calcitriol and calcidiol step by step. The end product is calcitroic acid, which is excreted via the bile. Source 1, 4

Cofactors in this pathway

• Magnesium — Described as a cofactor of the enzymes that convert vitamin D in liver and kidney, and of the binding protein Source 5In the ORY catalogue as a laboratory value: Magnesium
• NADPH — Electron donor for CYP2R1, CYP27B1 and CYP24A1 Source 1
• Iron — Haem iron at the centre of the cytochrome P450 enzymes that convert vitamin D Source 1, 2In the ORY catalogue as a laboratory value: Eisen
• Zinc — Forms the zinc fingers with which the vitamin D receptor binds to DNA Source 6In the ORY catalogue as a laboratory value: Zink
• Vitamin A (retinoic acid) — Binds to RXR, the partner of the vitamin D receptor Source 6
• Calcium — Transported across the intestinal wall via the gene products TRPV6 and calbindin Source 2In the ORY catalogue as a laboratory value: Calcium (intrazellulär)

Sources

1. Bikle DD. Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol 2014 · PubMed 24529992
2. Christakos S, Dhawan P, Verstuyf A et al. Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects. Physiol Rev 2016 · PubMed 26681795
3. Holick MF, MacLaughlin JA, Clark MB et al. Photosynthesis of previtamin D3 in human skin and the physiologic consequences. Science 1980 · PubMed 6251551
4. Saponaro F, Saba A, Zucchi R. An Update on Vitamin D Metabolism. Int J Mol Sci 2020 · PubMed 32911795
5. Uwitonze AM, Razzaque MS. Role of Magnesium in Vitamin D Activation and Function. J Am Osteopath Assoc 2018 · PubMed 29480918
6. Haussler MR, Haussler CA, Jurutka PW et al. The vitamin D hormone and its nuclear receptor: molecular actions and disease states. J Endocrinol 1997 · PubMed 9379138

Whole pathway: Vitamin D

Related pathways

• Calprotectin — Eisen, Zink
• Estradiol — Magnesium, Eisen
• HbA1c and insulin — Magnesium, Zink
• Neopterin — Magnesium, Eisen
• 8-OHdG — Eisen, Zink

As of 2026-09-16. Draft written by Claude to schema v2; sources checked in PubMed; expert review pending
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