Photolysis, 7-dehydrocholesterol

Vitamin D is obtained in the diet or by photolysis of 7-dehydrocholesterol in skin exposed to sunlight. Calcitriol works in concert with parathyroid hormone in Ca2+ homeostasis, regulating [Ca2+] in the blood and the balance between Ca2+ deposition and Ca2+ mobilization from bone. Acting through nuclear receptors, calcitriol activates the synthesis of an intestinal Ca2+-binding protein essential for uptake of dietary Ca2+. Inadequate dietary vitamin D or defects in the biosynthesis of calcitriol result in serious diseases such as rickets, in which bones are weak and malformed (see Fig. 10-20b). 

Vitamin D3 is a precursor of the hormone 1,25-dihy-droxyvitamin D3. Vitamin D3 is essential for normal calcium and phosphorus metabolism. It is formed from 7-dehydrocholesterol by ultraviolet photolysis in the skin. Insufficient exposure to sunlight and absence of vitamin D3 in the diet leads to rickets, a condition characterized by weak, malformed bones. Vitamin D3 is inactive, but it is converted into an active compound by two hydroxylation reactions that occur in different organs. The first hydroxylation occurs in the liver, which produces 25-hydroxyvita-min D3, abbreviated 25(OH)D3 the second hydroxylation occurs in the kidney and gives rise to the active product 1,25-dihydroxy vitamin D3 24,25 (OH)2D3 (fig. 24.13). The hydroxylation at position 1 that occurs in the kidney is stimulated by parathyroid hormone (PTH), which is secreted from the parathyroid gland in response to low circulating levels of calcium. In the presence of adequate calcium, 25(OH)D3 is converted into an inactive metabolite, 24,25 (OH)2D3. The active derivative of vitamin D3 is considered a hormone because it is transported from the kidneys to target cells, where it binds to nuclear receptors that are analogous to those of typical steroid hormones. l,25(OH)2D3 stimulates calcium transport by intestinal cells and increases calcium uptake by osteoblasts (precursors of bone cells). 

Sunlight is not strictly essential for cutaneous synthesis of cholecalciferol, because UV-B penetrates clouds reasonably well complete cloud cover reduces the available intensity by about 50%. It also penetrates light clothing. However, low-intensity irradiation (below 20 ml per cm in vitro) does not result In significant photolysis of 7-dehydrocholesterol to previtamin D. Acute whole-body exposure to UV-B irradiation below 18 ml per cm does not result in any detectable increase in plasma cholecalciferol or calcidiol. In temperate regions (beyond about 40°N or S), the intensity of UV-B is below this threshold in winter, so there is unlikely to be any significant cutaneous synthesis of the vitamin in winter, and plasma concentrations of calcidiol show a marked seasonal variation in temperate regions (Holick, 1995 see Table 3.2). 

The most abundant form of vitamin D is D3, called cholcalciferol. Vitamin D is not technically a vitamin, because it is not required in the diet. It arises from uv-photolysis of 7-dehydrocholesterol, an intermediate in cholesterol biosynthesis (see here). 

Vitamin D is produced in skin as a result of ultraviolet irradiation, a phenom enon realized in 1919—1924 It is known that ultraviolet light brings about a photolyas of 5,7-diene sterols giving rise to previtamin D and other photoisomers, lumisterol and tachysterol (Fig. 2). The previtamin D spontaneously isomerizes to vitamin D to yield an equilibrium mixture favoring vitamin D. This photolysis known to occur in organic solvents also occurs in epidermis of skin. Ultraviolet light is known to penetrate to the site of 7-dehydrocholesterol in epidermis Recently, the antirachitic substance produced in rat skin by ultraviolet irradiation has been isolated in pure form and unequivocally identified as vitamin D3 The... 

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. 

The synthesis of Vitamin D3 in vivo takes place in the skin. UV-B radiation ( = 290-315 nm) cleaves 7-dehydrocholesterol, an intermediate product of cholesterol metabolism, in the epidermis, which isomerises spontaneously at body temperature to cholecalciferol. While the photolysis is very efficient, it is subject to seasonal and climatic fluctuations. Strong pigmentation and aged skin lead to a considerably reduced capacity to produce Vitamin D. 

The hydroxy-group of cholesterol is protected either as the acetate or benzoate. Bromination in the allylic position by Karl Zieglers method using N-hro-mosuccinimide or l,3-dibromo-5,5-dimethylhydantoin, then dehydrobromina-tion with 2,4,6-collidine and hydrolysis gives 7-dehydrocholesterol. Photolysis of 7-dehydrocholesterol and ergosterol, respectively, with a mercury vapour lamp in an inert solvent (e.g. peroxide-free diethyl ether, methanol, cyclohexane... 

Cholecalciferol (vitamin D3) is formed by photolysis of 7-dehydrocholesterol, a precursor in cholesterol biosynthesis. As shown in Fig. 3.42, UV radiation opens the B ring. The precalciferol formed is then isomerized to vitamin D3 by a rearrangement of the double bond which is influenced by temperature. Side-products, such as lumi- and tachisterol, have no vitamin D activity. Cholecalciferol is converted into the active hormone, 1,25-dihydroxy-cholecalciferol, by hy-droxylation reactions in liver and kidney. 7-Dehydrocholesterol, the largest part of which is supplied by food intake and which accumulates in human skin, is transformed by UV light into vitamin D3. The occurrence and the physiological significance of the D vitamins are covered in Sect. 6.2.2. 

Cholecalciferol (vitamin D3, I) is formed from cholesterol in the skin through photolysis of 7-dehydrocholesterol (provitamin D3) by ultraviolet light ( sunshine vitamin cf. 3.8.2.2.2). Similarly, vitamin D2 (ergocalciferol, II cf. Formula 6.2) is formed from ergosterol. 

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