Calciferols vitamin 7-dehydrocholesterol

Vitamin D is the collective term for a group of compounds formed by the action of ultraviolet irradiation on sterols. Cholecalciferol (vitamin D3) and calciferol (vitamin D2) are formed by irradiation of the provitamins 7-dehydrocholesterol and ergosterol, respectively. The conversion to vitamin D3 occurs in the skin. The liver is the principal storage site for vitamin D, and it is here that the vitamin is hydroxylated to form 25-hydroxyvitamin D. Additional hydroxylation to form 1,25-dihydroxyvita-min D occurs in the kidney in response to the need for calcium and phosphate. A discussion of the role of vitamin D in calcium homeostasis is provided in Chapter 66. 

However, it was not until 1924, when Steenbock and Hess showed that irradiation of certain foods generated protective activity against the disease, that vitamin D (calciferol) was recognized as a second lipid-soluble vitamin. Vitamin D is a family of compounds formed by the irradiation of A5/7-unsaturated sterols such as ergosterol and 7-dehydrocholesterol. The former yields ergocalciferol (vitamin D2) and the latter cholecalciferol (vitamin D3). 

As a brief introductory summary, vitamin D substances perform the following fundamental physiological functions (1) promote normal growth (via bone growth) (2) enhance calcium and phosphorus absorption from the intestine (3) serve to prevent rickets (4) increase tubular phosphorus reabsorpiion (5) increase citrate blood levels (6) maintain and activate alkaline phosphatase m bone (7) maintain serum calcium and phosphorus levels. A deficiency of D substances may be manifested in the form of rickets, osteomalacia, and hypoparathyroidism. Vitamin D substances are required by vertebrates, who synthesize these substances in the skin when under ultraviolet radiation, Animals requiring exogenous sources include infant vertebrates and deficient adult vertebrates, Included there are vitamin D (calciferol ergocalciferol) and vitamin D< (activated 7-dehydrocholesterol cholecalciferol). 

The most important or at least the best-known members of the family of D vitamins are vitamin D2 (calciferol), which is indicated in abbreviated form in Structure 1 and can be produced by ultraviolet irradiation of ergosterol, and vitamin D3 [Structure 2], which may be produced by the irradiation of 7-dehydrocholesterol. 

In 1918, Mellanby produced experimental rickets in dogs. In 1919, Huldschinsky ameliorated rachitic symptoms in children with ultraviolet radiation. Hess, in 1922, showed that liver oils contain the same antirachitic factor as sunlight In that same year, McCollum increased calcium deposition in rachitic rats with cod liver oil factor. In 1924. Steenbook and Hess demonstrated irradiated foods have antirachitic properties, It was in 1925 that McCollum named antirachitic factor as vitamin D. In 1931, Angus isolated crystalline vitamin D (calciferol). In 1936, Windaus isolated vitamin D3 (activated 7-dehydrocholesterol). 

The other exception is vitamin D3, or chole-calciferol. Assuming adequate sunlight, chole-calciferol is the photochemical product from ultraviolet irradiation of 7-dehydrocholesterol found in our skin. A significant proportion of the world s population produces all of the cholecalciferol it needs from this photochemical reaction. It is true that a photochemical reaction is not a biochemical pathway, but exposure to adequate sunlight does fulfill the requirement for cholecalciferol. As noted in the discussion for this particular substance, the compounds commonly referred to as vitamins Dg and D3 are not normal constituents of most human diets. 

Vitamin D is unique in that it can be either obtained from the diet (as vitamin D2 or D3) or synthesized from a cholesterol precursor, a process that requires reactions in the skin, liver, and intestine. The calciferols, including several forms of vitamin D, are a family of steroids that affect calcium homeostasis (Fig. 34.26). Cholecalciferol (vitamin D3) requires ultraviolet light for its production from 7-dehydrocholesterol present in cutaneous tissues (skin) in animals and from ergosterol in plants. This irradiation cleaves the carbon-carbon bond at C9-C10 to open the B ring to form cholecalciferol, an inactive precursor of l,25-(OH)2-cholecalciferol (calcitriol). Calcitriol is the most potent biologically active form of vitamin D (see Fig. 34.26). 

Calcium-regulating sterols control the resorption of calcium ions into the gastro-intestinal tract, and influence bone metabolism. Vitamin D3 (chole-calciferol), generated by photolysis of 7-dehydrocholesterol, is its most prominent member. 

Both are equally effective In man, and the latter Is often placed In the class of hormones since calciferol Is formed by the action of sunlight on 7-dehydrocholesterol In the skin (Frleden and Llpner, 1971) Vitamin D Increases bone sensitivity to parathyroid hormones and promotes Intestinal absorption of calcium and phosphate ... 

Vitamin D consists of a group of sterol derivatives produced by ultraviolet irradiation of the corresponding precursors. The two important members of this group are vitamin D2 or calciferol, which is activated ergosterol, and vitamin D3, which is activated 7-dehydrocholesterol. The latter is the compound formed in the skin on exposure to sunshine or ultraviolet rays. 

A group of fat-soluble vitamins. Cholecalciferol (vitamin D3) can be obtained from dietary sources and can also be produced in the skin by the action of sunlight on 7-dehydrocholesterol. Another vitamin D (ergocalciferol, vitamin Dj) can be obtained from plants. Cholecalciferol undergoes two hydroxylation steps in the body in its conversion to its active form, 1,25-dihydroxy-cholecalciferol. The C-2S hydroxylation takes place in the liver and this is followed by the C-I hydroxylation which takes place in the kidneys. The rate of synthesis of 1,25-dihydroxychole-calciferol is thought to be controlled by the circulating parathyroid hormone levels. 

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... 

Calciferol is the anti-rachitic steroid obtained artificially. It was first regarded as being identical with vitamin D, and ergosterol was accepted as being the natural provitamin. However, in 1934, Waddell found that both irradiated cholesterol and cod-liver oil concentrates were more effective than calciferol, when given in equivalent dosage to rachitic chickens, and now it is believed that several different vitamins of the D type exist, including D, the anti-rachitic factor in natural liver oils, Dg, or calciferol, and Dg, the factor obtained from 7-dehydrocholesterol, which is its provitamin in crude cholesterol. 

It was thought at first that calciferol, the synthetic vitamin obtained from ergosterol, was indentical with the natural vitamin D, but Bills showed that calciferol was less potent, and, subsequently, a third form of the anti rachitic vitamin was obtained from dehydrocholesterol, a naturally occunii sterol, and it seems probable that other forms exist. In current nomenclature, vitamin D is the natural vitamin present in liver oils vitamin D is calciferol, the irradiation product from ergosterol and vitamin Dj is the vitamin obtained by the irradiation or chemical activation of dehydrocholesterol. A fourth form of the vitamin, D, has been obtained artificially by irradiation of 22, 23-dehydroergosterol (Windaus, 1937). 

Vitamin D, also called calciferol, is related to the steroids. It arises from A - -un-saturated sterols, the provitamins, by ultraviolet irradiation (cf. the diagram of formulas in Chapt. XIV-4). Thus, vitamin D2 (ergocalciferol) arises from ergos-terol vitamin D3 (cholecalciferol) from A -dehydrocholesteroI. In this connection it is important that A -dehydrocholesterol is concentrated in the skin and therefore exposed to irradiation. 

Vitamin D is composed of a number of related stmc-tures but the two most prominent members of the family are colecalciferol and ergocalciferol, which is formed from ergosterol rather than 7-dehydrocholesterol. Cole-calciferol is transformed into the most active form of the vitamin, 1,25-dihydroxycholecalciferol, by hydroxylation at the 25 position in the liver and finally at the 1 position in the kidneys. 

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