Vitamin D3 - Cholecalciferol

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. 

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 D3 (cholecalciferol or calciol), from irradiation of 7-dehydrocholesterol... 

AOAC official method 992.26. Vitamin D3 (cholecalciferol) in ready-to-feed milk-based infant formula. Liquid chromatographic method. In MP Bueno, ed. Official Methods of Analysis of AOAC International. 16th ed. Arlington, VA AOAC International, 1995, p. 50-5-50-6. 

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-... 

Vitamin D is a secosteroid produced in the skin from 7-dehydrocholesterol under the influence of ultraviolet irradiation. Vitamin D is also found in certain foods and is used to supplement dairy products. Both the natural form (vitamin D3, cholecalciferol) and the plant-derived form (vitamin D2, ergocalciferol) are present in the diet. These forms differ in that ergocalciferol contains a double bond (C22-23) and an additional methyl group in the side chain (Figure 42-2). In humans this difference apparently is of little physiologic consequence, and the following comments apply equally well to both forms of vitamin D. 

Cholesterol is involved in two major biological processes. It is a structural component of cell membranes (Chap. 6) and the parent compound from which steroid hormones, vitamin D3 (cholecalciferol), and the bile salts are derived. Cholesterol is synthesized de novo in the liver and intestinal epithelial cells and is also derived from dietary lipid. De novo synthesis of cholesterol is regulated by the amount of cholesterol and triglyceride in the dietary lipid. 

The fat-soluble vitamins include vitamin A (retinol), a colorless compound resulting from cleavage of /3-carotene, vitamin D3 (cholecalciferol) a steroid, and vitamins E and K (tocopherols and menadione and their derivatives, respectively), which consist of isoprene and phenolic-quinone components. 

The cycloaddition of 4-phenyl-3//-l,2,4-triazole-3,5(4//)-dione to vitamin D3 (cholecalciferol) occurs regioselectively with the more reactive, least substituted diene. Different ratios of dia-stereomeric f)- and a-adducts 12 were obtained by different authors by working in ethyl acetate7 and in dichloromethane8, although the -adduct always predominated. The diastereoselectivity ratio drops to 1 in the cycloaddition of 4-phenyl-3//-1,2,4-triazole-3,5(47/)-dione to (5 )-chole-calciferol, where the reactive s-cw-diene is more remote from the bicyclic moiety7. Cycloreversion of both adducts by base treatment affords only (5 )-cholecalciferol. 

There are various physiological forms known as vitamins D, namely vitamin D2 (calciferol, ergocaldferol), vitamin D3 (cholecalciferol), phosphate esters of D2, D3, 25-hydroxycholecalciferol, 1,25-dihydroxychole-caldferol, and 5,25-dihydroxycholecalciferol. There are active anologs and related compounds known as vitamins D, namely 22-dihydroergosterol (vitamin D4), 2-dehydrostigmasterol (vitamin Dg), and 7-dehydro-sitosterol (vitamin D5) [3]. 

Vitamin D occurs in a number of sterol forms, such as vitamin D3 - cholecalciferol - a natural form in foods and made in the skin by the action of UV, and vitamin D2 -ergocalciferol - which is formed in plants by the action of sunlight. These forms are 25-hydroxylated in the kidney, and then la-hydroxylated in the kidney (under the control of parathormone), to make the most active form. This is available as calcitriol (la,25-dihydroxycholecalciferol). Vitamin D facilitates the absorption of calcium and, to a lesser extent, phosphorus from the intestine and promotes deposition into the bones. A deficiency of vitamin D, therefore, results in bone deficiency disorders, e.g. rickets in children. Good food sources include eggs, milk and cheese. 

Trivedi DR Doll R, Khaw KT. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community Randomised double blind controlled trial. BMJ 2003 326 469. 

Vitamin D is associated with biological functions, such as bone formation, immune system responses, cell defences and anti-tumour activity.615,616 Vitamin D comes in two closely related forms, vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol), and their metabolites. Both vitamin D2 and D3 occur naturally in some foods. However, vitamin D3 (63) can also be synthesized in skin cells called keratinocytes from 7-dehydrocholesterol (provitamin D 64), which undergoes a photochemical six-electron conrotatory electrocyclic ring opening at 280nm to previtamin D3 (41 see also Scheme 6.8), which spontaneously isomerizes to 63 in a thermal antarafacial hydride [l,7]-sigmatropic shift (Scheme 6.21). Both vitamin D2 and D3 are subsequently converted to active hormone 1,25-D by enzymes in several steps. The recommended daily intake of vitamin D for humans is 5 10 pg per day. For example, 15 ml of fish liver oils and 100 g of cooked salmon contain approximately 35 and 10 pg... 

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