Absorption Metabolism and Excretion of Vitamin D

Vitamin D (vitamin D without a subscript represents either vitamin D2 or D3) is fat soluble and, therefore, once ingested vitamin D2 and vitamin D3 are incorporated into the chylomicron fraction and absorbed in the small intestine into the lymphatic system. Both dietary vitamin D2 and vitamin D3, and cutaneous vitamin D3 enter the circulation and are bound to a specific a1-globulin known as the vitamin D-binding protein. It is believed that this protein acts as a buffering system whereby it helps maintain circulating concentrations of 25(OH)D so that the free unbound form of 25(OH)D can enter into the renal tubular cells to be metabolized.

Neither vitamin D2 nor vitamin D3 possess any intrinsic biologic activity on calcium metabolism. They both require a hydroxylation on carbon 25 to form 25(OH)D (Figure 4). 25(OH)D is the major circulating form of vitamin D and at physiologic concentrations it has little biologic activity on calcium metabolism. It must undergo a hydroxylation

7-Dehydrocholesterol (provitamin D3)

25 27

25 27

7-Dehydrocholesterol (provitamin D3)

Vitamin D3 (cholecalciferol)

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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