7-Dehydrocholesterol, vitamin

Figure 42-9. Formation and hydroxylation of vitamin D3.25-Hydroxylation takes place in the liver, and the other hydroxylations occur in the kidneys. 25,26(OH)2-D3 and 1,25,26(OH)3-D3 are probably formed as well. The formulas of 7-dehydrocholesterol, vitamin D3, and 1,25(OH)2-D3 are also shown. (Modified and reproduced, with...

Vitamin D3 (cholecalciferol) can be made in the skin from 7-dehydrocholesterol in the presence of ultraviolet light (see fig. 24.13). Vitamin D3 is formed by the cleavage of ring 3 of 7-dehydrocholesterol. Vitamin D3 made in skin or absorbed from the small intestine is transported to the liver and hydroxylated at C-25 by a microsomal mixed-... 

A flow diagram for the manufacturing process is shown in Figure 8. First, ether solution containing 7-dehydrocholesterol is recirculated through a quartz uv reactor, and the ether is distilled off. Methanol is added to the 7-dehydrocholesterol—vitamin mixture, and the remaining ether is... 

Vitamin D3 (cholecalciferol, Calcitol, activated 7-dehydrocholesterol, (+)-vitamin D3) [67-97-0] 384.6, m 83-85 , [a] Uj +126 (c 2, EtOH). It is converted into its 3,5-dinitrobenzoyI ester and crystallised repeatedly from acetone. The ester is then saportified and the free vitarrrin is isolated. Store it in sealed ampoules urtder argon below 8 . It acts through a receptor which modrrlates differerrtiation and proliferation of normal arrd neoplastic cells. [Laughland Phillips Anal Chem 28 817 1956, DeLuca Schones Ann Rev Biochem 52 411 1983, Beilstein 6 III 2811,6IV 4149 ]... 

The term vitamin D embraces two different substances calciferol, C28H43OH, Mol. Wt. 396 7 (vitamin Dg or activated ergosterol), and 7 dehydrocholesterol (vitamin D3). Both forms have similar chemical and... 

A steroid very closely related structurally to cholesterol is its 7 dehydro derivative 7 Dehydrocholesterol is formed by enzymatic oxidation of cholesterol and has a conju gated diene unit m its B ring 7 Dehydrocholesterol is present m the tissues of the skin where it is transformed to vitamin D3 by a sunlight induced photochemical reaction... 

See also 7-Dehydrocholesterol Cholecalciferol. [VITAMINS - VITAMIN D] (Vol 25) -See also 22,23-Dihydroergosterol. [VITAITINS - VITAMIN D] (Vol 25)... 

Infants maybe sensitive to doses of vitamin A [11103-57-4] in the range of 75,000—200,000 lU (22.5—60 mg), although the toxic dose in adults is probably 2—5 million lU (90.6—1.5 g). Intakes in this range from normal food suppHes without oral supplements are simply beyond imagination (79). Vitamin D [1406-16-2] toxicity is much more difficult to substantiate clinically. Humans can synthesize active forms of the vitamin in the skin upon irradiation of 7-dehydrocholesterol. Toxic symptoms are relatively nonspecific, and dangerous doses seem to He in the range of 1000—3000 lU/kg body wt (25—75 flg/kg body wt) (80). Cases of toxicity of both vitamins E and K have been reported, but under ordinary circumstances these vitamins are considered relatively innocuous (81). 

Vitamins are classified by their solubiUty characteristics iato fat-soluble and water-soluble groups. The fat-soluble vitamins A, E, and K result from the isoprenoid biosynthetic pathway. Vitamin A is derived by enzymic cleavage of the symmetrical C q beta-carotene, also known as pro-vitamin A. Vitamins E and K result from condensations of phytyldiphosphate (C2q) with aromatic components derived from shikimic acid. Vitamin D results from photochemical ring opening of 7-dehydrocholesterol, itself derived from squalene (C q). 

Vitamin (cholecalcifetol calciol), (5Z,7E)-(33)-9,10-seco-5,7,10(19) cholestatriene-3-ol (4), is the naturally occurring active material found ki all animals. It is produced ki the skin by the kradiation of stored 7-dehydrocholesterol (provitamin E) ), cholesta-5,7-diene-3B-ol (3). 

Windaus and Boch (13) isolated and characterized 7-dehydrocholesterol in 1937 from pig skin. They further showed that vitamin D could be generated from the provitamin by uv inradiation. 

P-Hydroxy steroids which contain the 5,7-diene system and can be activated with uv light to produce vitamin D compounds are called provitamins. The two most important provitamins are ergosterol (1) and 7-dehydrocholesterol (3). They are produced in plants and animals, respectively, and 7-dehydrocholesterol is produced synthetically on a commercial scale. Small amounts of hydroxylated detivatives of the provitamins have been synthesized in efforts to prepare the metaboHtes of vitamin D, but these products do not occur naturally. The provitamins do not possess physiological activities, with the exception that provitamin D is found in the skin of animals and acts as a precursor to vitamin D, and synthetic dihydroxalated... 

FIGURE 18.37 (a) Vitamin D3 (cholecalciferol) is produced in the skin by the action of sunlight on 7-dehydrocholesterol. The successive action of mixed-function oxidases in the liver and kidney produces 1,25-dihydroxyvitamin D3, the active form of vitamin D. 

Actually, neither vitamin D2 nor D3 is present in foods. Rather, foods contain the precursor molecules 7-dehydrocholesterol and ergosterol. In the presence of sunlight, however, both precursors are converted under the skin to the active vitamins, hence the nickname for vitamin D, the "sunshine vitamin. 7... 

The active vitamins are produced by conversion of provitamins by ultraviolet light. Ergosterol, a yeast sterol, is converted to its active form, ergocalciferol (vitamin D2), and 7-dehydrocholesterol, which is found in many natural foods and is also synthesized in man, is converted to cholecalciferol (vitamin D3). Fish liver oils are virtually the only source of vitamin D3 in nature. The most active form of vitamin D3 is 1,25-dihydroxycholecalciferol and this is produced by the hydroxylation of cholecalciferol at position 25 in the liver and then at position 1 in the kidney. 

Activation of 7-dehydrocholesterol by UV light in the skin produces cholecalciferoi (vitamin Dj) This step is insufficient in many people in cold, doudy dimates, and vitamin Dj... 

Vitamin D is commonly found in two forms, both derivatives of steroids. These are known as cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2). Cholecalciferol is formed directly from the steroid known as 7-dehydrocholesterol by the action of sunlight, or other source of ultraviolet (UV) light, in the skin of humans and other animals. When parents encourage their children to go out and play in the sun, there is good reason for doing so (but avoid sunburn). ... 

Vitamin D hormone is derived from vitamin D (cholecalciferol). Vitamin D can also be produced in the body it is formed in the skin from dehydrocholesterol during irradiation with UV light. When there is lack of solar radiation, dietary intake becomes essential, cod liver oil being a rich source. Metaboli-cally active vitamin D hormone results from two successive hydroxylations in the liver at position 25 ( calcifediol) and in the kidney at position 1 ( calci-triol = vit. D hormone). 1-Hydroxylation depends on the level of calcium homeostasis and is stimulated by parathormone and a fall in plasma levels of Ca or phosphate. Vit D hormone promotes enteral absorption and renal reabsorption of Ca and phosphate. As a result of the increased Ca + and phosphate concentration in blood, there is an increased tendency for these ions to be deposited in bone in the form of hydroxyapatite crystals. In vit D deficiency, bone mineralization is inadequate (rickets, osteomalacia). Therapeutic Liillmann, Color Atlas of Pharmacology... 

Blood levels of vitamin D are influenced both by dietary intake and the amount of daylight exposure to the skin. Indeed, exposure of the skin to ultraviolet light catalyzes the synthesis of vitamin D3 (cholecalciferol) from 7-dehydrocholesterol thus vitamin D is more like a hormone and not strictly a vitamin. Furthermore, the UV radiation catalyzes the synthesis of ergocalciferol from ergosterol. This latter compound is found in plants, especially yeast and fungi, but the conversion to ergocalciferol... 

Vitamin D is synthesized in the skin in the presence of ultraviolet light, and it is unusual to become dependent on dietary intake except when exposed to inadequate UV light. The active form of vitamin D is 1,25-dihydroxycholecalciferol (1,25-OHCC), also termed calcitriol. For vitamin D synthesis, cholecal-ciferol (also termed vitamin D3) is synthesized in the skin from cholesterol via 7-dehydrocholesterol, and is 25-hydroxylated in the liver and 1-hydroxylated in the kidney. Dietary vitamin D is actually a mixture of sterols which includes 7-dehydrocholesterol, and is mainly found in fish and eggs. 

The primary supply of vitamin in humans is not obtained from the diet but rather is derived from the ultraviolet photoconversion of 7-dehydrocholesterol to vitamin Ds in skin. Thus, vitamin Dj synthesis varies with the seasons. D3 is a prohormone and requires further metabolic conversion to exert biological activity in its target organs (Fig. 66.2). The liver and the kidney are the major sites of metabolic activation of this endogenous sterol hormone. The initial transformation of D3 occurs in the liver and is catalyzed by the enzyme 25-OH-D3-hydroxylase... 

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