Vitamin D

Vitamin D3 (cholecalciferol) is produced by ultraviolet irradiation of provitamin D3 (7-dehydrocholesterol) in the skin, and can also be obtained from dietary sources. Vitamin D2 (ergocalciferol) is produced by the ultraviolet irradiation of the plant sterol, ergosterol.

In the liver, vitamin D3 is converted by hydroxylation at the C-25 position to 25-hydroxyvitamin D3 (calcidiol).

In the kidneys, 25-hydroxyvitamin D3 is hydroxylated at the C-lalpha position to the hormonally active metabolite, 1,25-dihydroxyvitamin D3 (calcitriol). This reaction is catalysed by lalpha-hydroxylase in the proximal tubule cells, and

Ultraviolet light on skin

Diet

Vitamins D2 and D3 Vitamin D3

Liver

25-hydroxycholecalciferol Kidney

1, 25-dihydroxycholecalciferol 24, 25-dihydroxycholecalciferol (active metabolite)

Figure 10.6 Pathway for vitamin D synthesis.

promoted by PTH. Hydroxylation can also lead to 24, 25-dihydroxyvitamin D3. The biological activity of calcitriol is 100 times greater than that of 25-hydroxycholecalciferol.

The hydroxylases in the liver and kidneys are all cytochrome P450 mixed function oxidases. The most important control point is the activity of renal 1-hydroxylase, which modulates the production of 1,25 dihydroxyvitamin D3.

Calcitriol acts by binding to the nuclear vitamin D receptor, a 427 amino acid protein encoded by an 11 exon gene located at chromosome 12. It stimulates absorption or reabsorption of calcium in the small intestine, bone, and kidneys.

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