Vitamin D3 (cholecalciferol)

Ergosterol Vitamin D2

(provitamin D2) (ergocalciferol)

Figure 2 Structures for 7-dehydrocholesterol (provitamin D3), ergosterol (provitamin D2), vitamin D3 (cholecalciferol), and vitamin D2 (ergocalciferol). The carbons are numbered and the ring systems are labeled.

on carbon 1 in the kidney to form 1,25(OH)2D, the biologically active form of vitamin D (Figure 4). The metabolism of 25(OH)D to 1,25(OH)2D is tightly regulated by parathyroid hormone (PTH) and serum phosphorus levels (Figure 5). PTH and low serum phosphorus levels increase the production of 1,25(OH)2D.

25(OH)D and 1,25(OH)2D act as substrate for a 24-hydroxylase (an enzyme that attaches an hydroxyl on carbon-24), which is found in the kidney and other target tissues for 1,25(OH)2D. Once 1,25(OH)2D is hydroxylated on carbon 24, this is the first step in its degradation to a water-soluble acid, calcitroic acid (Figure 4). Whereas, vitamin D is excreted in the bile, calcitroic acid is excreted by the kidney.

There continues to be speculation and controversy as to whether the 24-hydroxylation of 25(OH)D and 1,25(OH^D to 24, 25-dihydroxyvita-min D and 1,24,25-trihydroxyvitamin D, respectively, has important physiologic functions other than simply initiating the degradation of both metabolites.

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