Vitamin D
Vitamin D is a generic term for a family of secosteroids that have affinity for the Vitamin D receptor, and are involved in the physiologic regulation of calcium and phosphate metabolism. Vitamin D is a hormone, the precursor of which is synthesized in the skin as an outcome of a photochemical reaction involving UV irradiation. An insufficiency of irradiation may be compensated by an exogenous provision of vitamin D3 (
cholecalciferol) or D2 (
ergocalciferol). Vitamin D is known to regulate calcium and phosphorous metabolism in animals and humans and it has now been firmly established that the biological efficacy of vitamin D depends upon its metabolic conversion to hydroxylated derivatives. Thus vitamin D3 is hydroxylated in vivo to 25-hydroxyvitamin D3 in the liver which in turn is converted into 1.alpha.,25-dihydroxyvitamin D3 in the kidneys. It is the latter compound which is now recognized as being the circulating hormonal form of vitamin D. Both vitamin D3 and vitamin D2 must be 25-hydroxylated in the liver as the first step in their conversion to the 1,25-dihydroxylated compounds, which are generally considered to be the physiologically active or hormonal forms of the vitamins, and to be responsible for what are termed the vitamin D-like activities, such as increasing intestinal absorption of calcium and phosphorous, mobilizing bone mineral and retaining calcium in the kidneys. Vitamin D3 is synthesized in human skin from 7-dehydrocholesterol and ultraviolet light. Vitamin D3, or its analog Vitamin D2, can be ingested from the diet, for example in fortified milk products. Vitamin D2 and D3 undergo hydroxylation first in the liver to 25-hydroxyvitamin D, then in the kidney to 1.alpha.,25-dihydroxycholecalciferol (also known as 1,25-dihydroxyvitamin D or calcitriol), which is the principal biologically active form of Vitamin D. The biological production of this active form of the vitamin is tightly physiologically regulated. Calcitriol is formed by the sequential hydroxylation of vitamin D3 at C-25 in the liver and at C-1 in the kidney. Various other analogs can be produced by hydroxylation at C-24 and C-26. Vitamin D3, cholecalciferol, is produced in the body when the skin which contains the provitamin 7-dehydrocholesterol is exposed to sunlight. Calcitriol functions primarily in intestinal calcium transport and bone calcium resorption. Abnormalities in the metabolism of calcitriol, as manifested by circulating levels of the compound, have been shown to play roles in the pathogenesis of a variety of diseases such as renal osteodystrophy, sarcoidosis and post-menopausal osteoporosis. It is well known that vitamin D plays an active role in the homeostatic mechanisms that control calcium metabolism. That is, this vitamin is involved in the precise control of the concentration of the calcium ion in plasma. Vitamin D maintains calcium levels in the normal range by stimulating intestinal calcium absorption. When intestinal absorption is unable to maintain calcium homeostasis, Vitamin D stimulates monocytic cells to become mature osteoclasts, which in turn mobilize calcium from bones. Vitamin D is transported to various sites in the body where it is activated. The activated forms of the vitamin act on the target tissues, thereby causing an increase in calcium content. The activation of vitamin D is regulated in a negative feedback system by plasma calcium. Vitamin D exerts its calcium regulating activity through both genomic and nongenomic pathways. Although the nongenomic pathways remain poorly characterized, the genomic responses are mediated through binding to the nuclear Vitamin D receptor (VDR). The VDR is a ligand-activated transcription factor, which binds the Vitamin D3 response element contained within the promoter/enhancer region of target genes. The symptoms of these vitamin D deficiencies are most clearly apparent at bone level: rickets, osteomalacia and possibly participation in the phenomena of osteoporosis. There are other, less obvious associated disorders, for example an immune deficiency and a higher incidence of certain cancers and of vascular and endocrine disorders. Exposure to the sun and dietary intake are common sources of Vitamin D, but deficiencies of this vitamin can cause rickets and osteomalacia. Supplementation of dairy and other food products has reduced the incidence of Vitamin D deficiency conditions in modern society, and medical research concerning this vitamin has turned to its therapeutic effects in a variety of pathological conditions.
Vitamin D categories
Vitamin D2 (ergocalciferol)
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