Vitamin D: Metabolism
Section snippets
Synthesis of 1,25(OH)2D3 from vitamin D3
Vitamin D3 (cholecalciferol) is taken in the diet (from fortified dairy products and fish oils) or is synthesized in the skin from 7-dehydrocholesterol by ultraviolet irradiation. The vitamin D produced by 7-dehydrocholesterol depends on the intensity of UV irradiation, which varies with season and latitude.1 Sunscreen and clothing have been reported to prevent the conversion of 7-dehydrocholesterol to vitamin D3.2, 3 To be biologically active and affect mineral metabolism, and to have effects
Role of the vitamin D binding protein in vitamin D metabolism and action
Studies using mice deficient in DBP have resulted in new insight into the role of DBP in vitamin D metabolism and action. Although DBP null (−/−) mice have markedly lower total serum levels of 25(OH)D and 1,25(OH)2D3 than wild-type (WT) mice, the levels of serum calcium and PTH are normal in the DBP −/− mice.15 In patients with reduced levels of circulating DBP, serum calcium levels have also been reported to be normal.16 More recent studies using DBP null mice have shown that DBP is important
24-Hydroxylase (24(OH)ase)
In addition to 1,25(OH)2D3, the kidney can also produce 24,25-dihydroxyvitamin D3 (24,25(OH)2D3), a relatively inactive metabolite compared with 1,25(OH)2D3. 25-Hydroxyvitamin D3 24-hydroxylase (CYP24), also a mitochondrial P450 enzyme, can hydroxylate both 25(OH)D3 and 1,25(OH)2D3.5 It has been suggested that the preferred substrate for 24(OH)ase is 1,25(OH)2D3.18 Thus, 24(OH)ase limits the amount of 1,25(OH)2D3 in target tissues by accelerating the catabolism of 1,25(OH)2D3 to 1,24,25(OH)3D3,
By Calcium, Phosphate, PTH, and 1,25(OH)2D3
The widespread effects of 1,25(OH)2D3 necessitate a tight regulation of its bioavailability and a process of activation and deactivation that occurs through a series of negative and positive feedbacks, resulting in changes in the expression of the hydroxylase enzymes depending on the physiologic state.20, 21 Regarding regulation of vitamin D metabolism, low dietary calcium and phosphate result in enhanced activity of 1α(OH)ase (see Fig. 1).5 Elevated PTH resulting from hypocalcemia is a primary
Placenta
In pregnancy, the placenta regulates communication and transport between mother and fetus, with the placental trophoblasts and maternal decidua serving as the functional interface for exchange. 1α(OH)ase is expressed in both fetal trophoblast and maternal decidual cells beginning early in gestation.61 1α(OH)ase is most abundant in decidua.61 Synthesis of 1α(OH)ase is eightfold higher in first trimester decidual cells than in third trimester cells.62 This trend indicates an important role for
Vitamin D P450s in aging and chronic kidney disease
The capacity of the kidney to convert 25(OH)D3 to 1,25(OH)2D3 has been reported to decline with age. An increase in 24(OH)ase gene expression and an increase in clearance of 1,25(OH)2D3 with aging have been reported.66, 67, 68 These findings suggest that the combined effect of a decline in the ability of the kidney to synthesize 1,25(OH)2D3 and an increase in renal metabolism of 1,25(OH)2D3 may contribute to age-related bone loss.
Chronic kidney disease (CKD) has been shown to result in
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Studies referenced from the laboratory of S.C. were supported in part by NIH grant DK-38961-21.