Ergosterol and vitamin

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. 

WINDAUS, ADOLF (1876-1959). A German chemist who won the Nobel prize for chemistry in 1928. His work involved the study of steroids and the effect of ultraviolet light activity, ergosterol, and vitamin D2. He also researched digitalis and histamine. Although he studied medicine, he received his doctorate in chemistry at the University of Freiburg. 

This representation embraces the possibility of intermediate steps between ergosterol and vitamin D since ki refers to the slowest step and k can apply to any of these intermediate products. If y is the amount of vitamin D present at any time and c0 is the maximum possible content, it can be shown that... 

Vitamin D2 is mannfactured by UV-radia-tion of ergosterol and vitamin Dj is obtained from tuna fish liver oil and UV-radiation of 7-dehydrocholesterol. 

The syntheses of tt-complexes of a hormone, estron chromium tri-carbonyl, and a provitamin D, ergosterol, and vitamin A are reported. 

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. 

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). 

Ergocalciferol is formed from the plant sterol ergosterol by the action of UV light. It is ergocalciferol that is commonly found in vitamin pills and vitamin D-fortified foods. The biological activity of cholecalciferol and ergocalciferol is basically the same. 

In addition to the endogenous metabolites, some exogenous sterols possess biological activity similar to that of D3. Ergocalciferol (vitamin D2) is derived from the plant sterol ergosterol and may act as a substrate for both the 25-hydroxylase and the 1-hydroxylase enzyme systems of the liver and kidney to form 25-(OH)D2 and 1,25-(0H)2 D2, respectively. Ergocalciferol (vitamin D2) is the form used in commercial vitamins and supplemented dairy products. Dihydrotachysterol, another sterol that is used as a therapeutic agent, also functions as a substrate for the hydroxylase enzymes in the liver and kidney. 

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). 

Plants are significant to the diet of humans and animals since they provide most of the essential nutrients and vitamins. Vitamins C (ascorbic acid), E (a-tocopherol) and K (phylloquinone) are biosynthesized by plants, while (3-carotene, the precursor of vitamin A and ergosterol, the precursor of vitamin D, are also secondary plant metabolites. These metabolites are used in folk medicine and for industrial purposes, as raw materials for pharmaceutical and other products [3]. On the other hand, plants may produce substances, which are toxic and/or irritant to man. 

PRECURSOR. In biological systems, an intermediate compound or molecular complex present in a living organism which, when activated physiochemically, is converted to a specific functional substance. Sometimes the prefix pro is used to indicate that a compound in question plays the role of a precursor. Examples from the history of vitamin and other essential chemical developments include ergosterol (pro-vitamin D2), which is activated by ultraviolet radiation to form vitamin D carotene (provitamin A) is a precursor of vitamin A prothrombin forms thrombin upon activation in the blood-clotting mechanism. 

PROVITAMIN. The precursor of a vitamin. Examples are carotene and ergosterol, which upon activation become Vitamin A and Vitamin D, respectively. 

It was later discovered that vitamin D occurs in two active forms, ergocalciferol and cholecalciferol. Ergocal-ciferol is the synthetic form derived by the irradiation of ergosterol and is designated as vitamin (13,14). Cholecalciferol, the natural form, was identified (15,16) and designated as vitamin D3. Vitamins Do and °3 are equally active in humans and other mammals, Dut Dg is virtually inactive in poultry. 

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. 

I, 25-dihydroxyvitamin D j (1,25-dihydroxycholecalciferol). Activation of the receptor leads to expression of particular proteins, notably an intestinal Ca2+ binding protein, and regulation of intestinal Ca2+ uptake and Ca2+ sequestration in kidney and bone. Vitamin D2 (ergocalciferol) is industrially obtained from irradiation of yeast-derived ergosterol and is hydroxylated to form an active vitamin D receptor agonist. Vitamin D deficiency causes rickets. 

It is an interesting historical fact that the study of the photochemistry of conjugated dienes and trienes was initiated by the discovery of the photochemical transformation of ergosterol to vitamin D—a system... 

Vitamin D2 and vitamin are the two economically important forms of vitamin D. The other D vitamins have relatively Htde biological activity and are only of historical interest. Vitamin D2 (ergocalciferol ercalciol), (5Z,7E,22E)-(3S)-9,10-j 0-5,7,10(19)-22-ergostatraene-3-ol (2), is active in humans and other mammals, although recently (ca 1997) it has been shown to be less active than vitamin in catde, swine, and horses. It is relatively inactive in poultry. It is prepared by the uv kradiation of ergosterol (provitamin 11)2), (24-methylcholesta-5,7,22-triene-3B-ol (1), a plant sterol. 

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. 

Dehydrogenation. Windaus introduced use of mercuric acetate as a reagent for the dehydrogenation of specific unsaturated compounds eariy in his classicai investigations of ergosterol and the D vitamins. He had converted ergosterol (I)... 

Figure 49-17 Structure of vitamin D3 (choiecalciferol) and vitamin D2 (ergocalciferol) and their precursors. 7-Cholecalciferol is produced in the skin from 7-dehydrocho esterol on exposure to sunlight. Ergocalciferol is produced commercially by irradiation of ergosterol. (Modified from Holick MF,AdamsJS.Vitamin D metabolism and biological function. ln Avioli LV, Krone SM, eds. Metabolic bone disease, 2nd ed. Philadelphia WB Saunders, 1990 155-95.)...

FIGURE 18-6 Chemical structures of major sterols and cholesterol derivatives. The major sterols in animals (cholesterol), fungi (ergosterol), and plants (stigmasterol) differ slightly in structure, but all serve as key components of cellular membranes. Cholesterol is stored as cholesteryl esters in which a fatty acyl chain (R = hydrocarbon portion of fatty acid) is esterified to the hydroxyl group. Excess cholesterol is converted by liver cells into bile acids (e.g., deoxycholic acid), which are secreted into the bile. Specialized endocrine cells synthesize steroid hormones (e.g., testosterone) from cholesterol, and photochemical and enzymatic reactions in the skin and kidneys produce vitamin D. 

Ergosterol is the provitamin of vitamin D2, which differs from 7-dehy-drocholesterol and vitamin D3, respectively, only by having a double bond between C22 and C23 and a methyl group at C24. Vitamin D2 is the constituent in many commercial vitamin preparations and in irradiated milk and bread. The antirachitic potencies of D2 and D3 in humans are equal, but both must be converted to 25-(OH)-cholecalciferol and eventually to the active form calcitriol (1,25-(0H)2D3) for biologic activity. 

Dehydrocholesterol can be converted into the most active form — vitamin D3 (cholecalciferol). Ergosterol and 7-dehydrocholesterol are clearly identified as provitamin D because, after irradiation of the skin with UV light or exposure to sunlight, they can be converted into the active vitamin D2 and D3 forms (Fraser, 1980). 

The photochemical isomerization of trans-viidimm D3 to the cis isomer has been achieved under conditions where the vitamin was tethered to a silica gel substrate. A continuous photoreactor has been described for the photochemical conversion of ergosterol into vitamin T>2P Saltiel et alP have studied the isomerization within the 25-hydroxytachysterol and the 25-hydroxyprevitamin D3 systems shown in Scheme 3. The study used a two-stage irradiation at 254nm to 313 nm, and this results in conformer-specific photoconversion. 

Vitamin D Vitamin D is produced when ultraviolet light (UV) shines on the skin and triggers the conversion of a steroid known as ergosterol to vitamin D. Its major role is to help the body use calcium, and a deficiency causes rickets in children, the same condition caused by calcium deficiency. Vitamin D supplements are rarely needed, except by those who are almost never exposed to the sun. Both vitamin A and vitamin D are essential to normal growth and development. Overdosage of vitamin D can have serious consequences, however. Calcium deposits can form in the kidney, lungs, or tympanic membrane of the ear (leading to deafness). Infants and small children are especially susceptible to vitamin D toxicity. 

---