The characteristic bone deformities caused by vitamin D deficiency were most common in the industrial cities of the nineteenth century. In Boston, around 1900, approximately 80% of poor children suffered from bone deformities. Symptomatic treatment with cod liver oil and natural sunlight was not discovered until 1919. Another 20 years were needed until in vitro synthesis of this vitamin became possible, permitting large-scale prophylaxis.
The vitamin D family includes a number of compounds, all of which have vitamin activity. The most important compound in animals is vitamin D3 (chole-calciferol) which forms from 7-dehydrocholesterol (A) under the influence of light. Plants contain traces of the provitamin ergosterol. Its metabolite, vitamin D2 differs from D3 only by one double bond and one methyl group and has the same vitamin activity. Amounts are given in international units: 1 1U is equivalent to 0.025 |ag, 1 ]ag vitamin D3 or D2 = 40 1U.
Hydroxylation in the liver at C25 yields the intermediate 25-hydroxy-chole-calciferol. This is transformed into the active form of the vitamin by further hydroxylation at C1 to 1,25-dihydroxy-cholecalciferol (1,25-(OH)2-D3), a steroid hormone. Additionally, a multitude of synthetic vitamin D analogues exist that are used for the treatment of disturbances in Ca homeostasis. Strictly speaking, vitamin D is not a vitamin for humans since under favorable conditions sufficient amounts of it can be endogenously synthesized during sun exposure. The 7-dehydro-choles-terol made from cholesterol is converted to provitamin D3 in the skin under UV exposure, which turns into active vitamin D3 under the influence of heat (B).
Since vitamin D from foods is fat-soluble, it is transported to the liver in chylomicrons. All free vitamin D metabolites are transported in the blood, as well as in the liver, by a specific, vitamin D-binding protein (DBP). 1n the mitochondria of the renal proximal tubular cells, 1,25-(OH)2-D is hydroxylated a second time, this time at C24, by another enzyme. In case of over-supply of 1,25-(OH)2-D this pathway is favored, leading to inactivation of the hormone. The active 1,25-(OH)2-D reaches its target organs through the bloodstream where it circulates bound to proteins.
The last metabolic step, hydroxylation to 1,25-(OH)2-D, is strictly regulated: the presence of 1,25-(OH)2-D provides inhibiting feedback control (an alternative pathway to inactive 1,24-[OH]2-D is used). Parathormone and low phosphate levels activate the hydroxylating enzyme. A multitude of additional factors exert their influence mostly indirectly via parathormone: Ca, estrogen, glucocorticoids, and calcitonin among others. This tight regulation permits short-term adjustment depending on calcium and phosphate needs.
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