Antirachitic activity

The observation that the uv spectmm of provitamin D changed with uv inradiation and also produced antirachitic activity led to the conclusion that vitamin D was derived from the provitamin. Windaus found the vitamin D2 formula to be isomeric with the provitamins. 

The stability of vitamin D in fats and oils corresponds to the stability of the fat itself, as described previously for vitamin A. Vitamin D is, however, more stable than vitamin A under comparable conditions. Once freed from the protection of the food matrix, vitamin D is susceptible to decomposition by oxygen and light. The vitamin is stable towards alkali, but under conditions of even mild acidity the molecule isomerizes to form the 5,6-trans and isotachysterol isomers, neither of which possesses any significant antirachitic activity (42). 

The chicken egg yolk, as deduced from its antirachitic activity, contains 1-2 pg of cholecal-ciferol and this can be raised further by increasing the intake of vitamin D3 of the laying hen (94). The concentration in yolk is 5-10 times higher than that of total vitamin D3 plus its metabolites in blood plasma of normal chickens and 50-100 times higher than the concentration in any other tissue (95). Consequently, the chicken egg yolk is a potent source of vitamin D3. 

Because several of the metabolites of vitamin D3 are biologically active, the molecular species of vitamin D3 which passes into the yolk cannot be determined just from measurement of antirachitic activity. Consequently, a reliable and sensitive method for determining the amount of the unchanged form of vitamin D3 would be extremely beneficial to those interested in the metabolism and other factors that influence the chicken to deposit vitamin D3 in... 

Dihydrotachysterol has slight antirachitic activity. It increases the calcium concenuation in the blood, an effect for which tachysterol is only one tenth as active. In high doses, dihydrotachysterol is mote effective than the other analogues... 

A few years later Pfordte (89) adduced evidence to show that the total toxicity of crude Irradiation mixtures of ergosterol does not exceed the toxicity of equal amounts of vitamin D. Although he was able to obtain two fractions enriched In toxicity and showing very diminished antirachitic activity, the absolute toxicity was smaller by a factor of 10 or more (78, 89) than the toxlsterol described by Llnsert. Attempts to enhance the toxic activity by further purification failed. 

A number of analogues with other substituents in the benzene ring, such as p- ,p-C, 3,4-(OMe)2, and 2,4-Cl2, have been claimed to have antirachitic activity [349]. The 2-carboxymethylthio-4-amino-5-(/>-chlorophenyl)pyrimi-dine analogue was found to be very active against vaccinia virus [350] (see Part I, Volume 6, of this review for further information). 

The main metabolic pathway of C. proceeds through 23- and 26-hydroxylation to 23S,26-dihydroxycal-citriol and further oxidation to calcitriol-26,23-lactone. In total over SO metabolites of calciol and ercalciol have been isolated and identified to date. Most of these secondary products have no or a very reduced antirachitic activity but do possess other interesting physiological properties the relevance of which is being investigated. 

The D-vitamins are a group of fat soluble materials with high antirachitic activity. Rickets is a disease of infancy caused by faulty calcium hydroxy apatite deposition in the growing bone. It was Palm 140) in 1890 who found that the disease responded favorably to irradiation of patient s food or skin by sunlight or ultraviolet light. Mellanby 113) in 1919 first reported the presence of an antirachitic factor in cod-liver oil. This discovery encouraged research on the isolation of the active principle in fish-liver oil, but the low natural concentration of the vitamin made isolation very difficult. 

Vitamin D is necessary in the diet for the prevention of rickets, a disease involving malformation of the bones and unsatisfactory development of the teeth. There are several substances with antirachitic activity. The form that occurs in oils from fish livers is called vitamin D3 it has the following chemical structure ... 

A fat-soluble factor that counteracts the disturbance in bone development called rickets was separated from fat-soluble A by McCollum in 1922. Ultraviolet irradiation was soon found to produce antirachitic activity. Several substances are now known to have vitamin D activity, and structures have been ascertained for the more important ones. Calciferol or vitamin Ds is the principal one obtained by irradiation, while vitamin Da is the naturally occurring activated 7-dehydro-cholesterol. 

Vitamin D is another fat-soluble vitamin that does not totally conform to the traditional definition of a vitamin, because the body is able to synthesize this compoimd. Two compoimds are involved, ergocalciferol (vitamin D2) derived from the plant steroid ergosterol and cholecalciferol (vitamin D3), which is formed in the skin in response to sunlight. The main activity of vitamin D in the body is related to the maintenance of calcium homeostasis and exhibits antirachitic activity. In foods, vitamin D... 

In 1924, the mystery of how sunlight could prevent rickets was partially solved. Dr. Harry Steenbock of the University of Wisconsin and Dr. A. Hess of Columbia University, working independently, showed that the antirachitic activity could be produced in foods and in animals by ultraviolet light. The process, known as the Steenbock Irradiation Process was patented by Steenbock, with the royalties assigned to the Wisconsin Alumni Research Foundation of the University of Wisconsin. Subsequent research disclosed that it was certain sterols in foods and animal tissues that acquired antirachitic activity upon being irradiated. Before irradiation, the sterols were not protective against rickets. 

Although the precursors are activated by ultraviolet light, excessive irradiation results in the formation of slightly toxic compounds that have no antirachitic activity. 

Steenbock and Black and Hess independently recognized that exposure of animals and their food to ultraviolet radiation imparted antirachitic activity. This led to the recommendation for the ultraviolet irradiation of foods as a means of fortifying them with vitamin D. This resulted in the addition of provitamin D to milk followed by ultraviolet irradiation. As soon as it was possible to commercially synthesize vitamin D in large quantities, it was added directly to milk and other foods. 

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