7-Dehydrocholesterol provitamin

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). 

In the biosynthesis of vitamin D substances, precursors include cholesterol (skin + ultraviolet radiation) in animals ergosterol (algae, yeast + ultraviolet radiation), Intermediates in the biosynthesis include preergocaldferol, tachysterol, and 7-dehydrocholesterol. Provitamins in very small quantities are generated in the leaves, seeds, and shoots of plants. In animals, the production site is the skin. Target tissues in animals are bone, intestine, kidney, and liver. Storage sites in animals are liver and skin. 

Vitamin D3 is not an essential exogenous micronutrient as such because it is made endogenously from a precursor in skin, 7-dehydrocholesterol (provitamin D3), by exposure to the high-energy ultraviolet B (UVB) photons (290-315 nm) of the solar spectrum [33]. The photons penetrate the epider-... 

Cholesterol is also the precursor of vitamin D, which plays an essential role in the control of calcium and phosphorus metabolism. 7-Dehydrocholesterol (provitamin D is photolyzed by the ultraviolet light of sunlight to previtamin D, ... 

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... 

Dehydrocholesterol, provitamin D cholesta-5, 7-dien-3fi-ok a zoosterol (see Sterols). Af, 384.6, m. p. 150°C, [a]n -114 (c = 1 in chloroform). D. occurs in relatively high concentrations in animal and human skin, where it can be converted to vitamin D3 by ultraviolet radiation. Prevention and cure of rickets by UV irradiation is due to this conversion. 

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. 

The provitamin D in animal skin had a side-chain that was identical to cholesterol, i.e., it did not contain either a double bond or methyl group on carbons 22-23 and 24, respectively, and was identified as 7-dehydrocholesterol (provitamin D3) (Figure 2). The vitamin Ds generated from ergosterol and 7-dehydrocholesterol were called ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3), respectively. 

Figure 2 Structures for 7-dehydrocholesterol (provitamin D3), ergosterol (provitamin D2), vitamin D3 (cholecalciterol), and vitamin Da (ergocalciferol). The carbons are numbered and the ring systems are labeled.

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... 

Provitamin D. The molecular extinction coefficient of 7-dehydrocholesterol at 282 nm is 11,300 and is used as a measure of 7-dehydro isomer... 

Chloroform-methanol extracts of Borrelia burgdorferi were used for the identification of lipids and other related components that could help in the diagnosis of Lyme disease [58]. The provitamin D fraction of skin lipids of rats was purified by PTLC and further analyzed by UV, HPLC, GLC, and GC-MS. MS results indicated that this fraction contained a small amount of cholesterol, lathosterol, and two other unknown sterols in addition to 7-dehydrocholesterol [12]. Two fluorescent lipids extracted from bovine brain white matter were isolated by two-step PTLC using silica gel G plates [59]. PTLC has been used for the separation of sterols, free fatty acids, triacylglycerols, and sterol esters in lipids extracted from the pathogenic fungus Fusarium culmorum [60]. 

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. 

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. 

Vitamin D is represented by cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2), which are structurally similar secosteroids derived from the UV irradiation of provitamin D sterols. In vertebrates, vitamin D3 is produced in vivo by the action of sunlight on 7-dehydrocholesterol in the skin. Vitamin D2 is produced in plants, fungi, and yeasts by the irradiation of ergosterol. On irradiation, the provitamins are converted to previtamin D, which undergoes thermal transformation to vitamin D. 

FIGURE 66.1 Vitamins D3 and D2 are produced by ultraviolet irradiation of animal skin and plants, respectively. The precursor of vitamin D3 in skin is 7-dehydrocholesterol, or provitamin D. In humans, the storage, transport, metabolism, and potency of vitamins D2 and D3 are identical, and the net biologic activity of vitamin D in vivo results from the combined effects of the hydroxylated derivatives of vitamins D2 and D3. 

Vitamin D-active substances are required in the diets of growing children and pregnant women, but normal adults receiving sufficient doses of sunshine can manufacture sufficient amounts of these compounds to meet their needs. Active vitamin D compounds can by synthesized in such individuals from 7-dehydro-cholesterol (see Table 6.2), an intermediate in cholesterol biosynthesis. Dietary sources also include cholecalciferol, which is produced from 7-dehydrocholesterol and ergosterol (Table 6.2). 7-Dehydrocholesterol and ergosterol are often referred to as provitamins. 

The precursors of vitamins D2 and D3 are ergosterol and 7-dehydrocholesterol, respectively. These precursors or provitamins can be converted into the respective D vitamins by irradiation with ultraviolet light. In addition to the two major provitamins, there are several other sterols that can acquire vitamin D activity when irradiated. The provitamins can be converted to vitamin D in the human skin by exposure to sunlight. Because very few foods are good sources of vitamin D, humans have a greater likelihood of vitamin D deficiency than of any other vitamin deficiency. Enrichment of some foods with vitamin D has significantly helped to eradicate rickets, which is a vitamin D deficiency disease. Margarine and milk are the foods commonly used as carrier for added vitamin D. 

Provitamin D. The molecular extinction coefficient of 7-dehydrocholesterol at 282 nm is 11,300 and is used as a measure of 7-dehydro isomer content of the provitamin (96,97). High pressure Hquid chromatography can also be used to analyze the provitamins. There are a variety of chemicals that show characteristic colors when reacted with the provitamins. Some of these are Hsted in Table 9. 

A-11 Ergosterol and pro-vitamin D, 7-dehydrocholesterol, in the skin have the same structure except ergosterol has one more double bond in the side chain between C22 and C23 and has one more methyl group at C24. Both the provitamin D and ergosterol are converted to active vitamin D by UV radiation. 

Animals can convert cholesterol to 7-dehydrocholesterol. 7-Dehydrocholesterol is a provitamin of vitamin D. The expjosure of one s body to sunlight results in the conversion of 7-dehydrocholesterol in the skin to cholccalciferol (vitamin Dj). The provitamin in both plants and animals is converted to vitamin D by ultraviolet light via identical chemical reactions that involve the opening of the steroid ring (Figures. 49 and 9.50). 

FIGURE 9.50 UV light is required for conversion of plant (ergesterol) and animal (7-dehydrocholesterol) forms of the provitamin to the vitamin. The plant form differs from the animal form, in that the side-chain contains a double bond and an extra methyl carbon. UV light results in conversion of both forms of provitamin to vitamin D, and D3, respectively. (The side-chain double bond of D2 is not reduced in the body, but it can be artificially reduced in the laboratory, where the product is called vitamin D4.) Hydroxylation is shown for Dj, but not for D2. 

In a classical sense, vitamin D3. the form produced in animals, is not a true vitamin" because it is produced in the skin from 7-dehydrochole.sterol by UV radiation in the range of 290 to 3(X) nm. 7-Dehydrocholesterol is produced from cholesterol metabolism. Only when exposure to sunlight is inadequate does vitamin Di become a vitamin in the historical. sense. Further, vitamin D3 is now termed a provitamin because it requires hydroxylation by the liver and the kidney to be fully active. 

Chemistry. There are two forms of vitamin D, and both are considered biologically equivalent. Irradiation of the major plant sterol, ergosterol, produces ergocalciferol, also known as vitamin Dg (Fig. 8.11).Because they are photochemical reactions and in contrast to enzyme-catalyzed biochemical reactions, the formation of cholecalciferol is not clean. Exposure of human skin to sunlight of295-300 nm converts 7-dehydrocholesterol to provitamin D,. The isomerization to cholecalciferol (vitamin Dg) is heat catalyzed. Continuous exposure to ultraviolet radiation from the sun results in the reversible formation of lumisterol... 

Figure 6.1 Absorption spectra of prototype alkenes and alkynes. Top 1,1 bicyclohexene280 ( ), provitamin D520 (7 dehydrocholesterol ), cycloocta 1,3,5 triene520 ( ), tetramethy...

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