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Vitamin D designates a group of closely related compounds that possess antirachitic activity. It may be supplied through the diet or by irradiation of the body. The two most prominent forms of vitamin D are ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3). Ergocalciferol is derived from a common plant steroid, ergosterol, whereas cholecalciferol (Illus. 1) is produced from the precursor 7-dehydrocholesterol, exclusively from animal products. The provitamin 7-dehydrocholesterol, derived from cholesterol or squalene, is synthesized in the body and present in large amounts in skin, the intestinal wall and other tissues. Vitamin D precursors have no antirachitic activity.
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Vitamin D, in the pure form, occurs as colorless crystals that are insoluble in water but readily soluble in alcohol and other organic solvents. Vitamin D can be destroyed by over-treatment with ultraviolet (UV) light and by peroxidation in the presence of rancidifying polyunsaturated fatty acids (PUFA). Like vitamins A and E, unless vitamin D3 is stabilized, it is destroyed by oxidation. Its oxidative destruction is increased by heat, moisture and trace minerals. There is less destruction of vitamin D3 in freeze-dried fish meals during drying, possibly because of decreased atmospheric oxygen. There is negligible loss of crystalline cholecalciferol during storage for one year or of crystalline ergocalciferol for nine months in amber-evacuated capsules at refrigerator temperatures.
Vitamin D from the diet is absorbed from the intestinal tract, and is more likely to be absorbed from the ileal portion in greatest amounts due to the longer retention time of food in the distal portion of the intestine (Norman and DeLuca, 1963). Vitamin D is absorbed from the intestinal tract in association with fats, as are all the fat-soluble vitamins. Like the others, it requires the presence of bile salts for absorption (Braun, 1986), and is absorbed with other neutral lipids via chylomicron into the lymphatic system of animals. It has been reported that only 50% of an oral dose of vitamin D is absorbed. However, considering that sufficient vitamin D is usually produced by daily exposure to sunlight, it is not surprising that the body has not evolved a more efficient mechanism for dietary vitamin D absorption (Collins and Norman, 1991). Effective treatment of rickets by rubbing cod liver oil on the skin indicates that vitamin D can be absorbed through the skin.
Presence of the provitamin 7-dehydrocholesterol in the epidermis of the skin and sebaceous secretions is well recognized. Vitamin D is synthesized in the skin of many herbivores and omnivores, including humans, rats, pigs, horses, poultry, sheep and cattle. However, little 7-dehydrocholesterol is found in the skin of cats and dogs (and likely other carnivores), and therefore little vitamin D is produced in the skin (How et al., 1995). For poultry, Tian et al. (1994) reported that skin of the legs and feet of chickens contains about 30 times as much 7-dehydrocholesterol (provitamin D3) as the body skin. The cholecalciferol formed by the UV irradiation of 7-dehydrocholesterol in the skin is absorbed and transported by the blood, primarily bound to gamma-globulin, and becomes immediately available for further metabolism (Imawari et al., 1976).
Some of the vitamin D3 formed in and on the skin ends up in the digestive tract as many ruminant animals consume the vitamin as they lick their skin and hair. Vitamin D undergoes a multiple series of transformations and multi-site interactions in the living system (Deluca, 1979). Vitamin D metabolism in ruminants begins prior to absorption in that rumen microbes are capable of degrading vitamin D to inactive metabolites (Sommerfeldt et al., 1983), which may explain the higher vitamin D requirements in ruminants.
Production and metabolism of vitamin D (both D2 and D3) necessary to activate the target organs are illustrated in Figure 1. Once in the liver, the first transformation occurs in which a microsomal system hydroxylates the 25-position carbon in the side chain to produce 25-hydroxy-vitamin D [25-(OH)D]. This metabolite is the major circulating form of vitamin D under normal conditions and during vitamin D excess (Littledike and Horst, 1982). The [25-(OH]D is then transported to the kidney on the vitamin D transport globulin, where it can be converted in the proximal convoluted cells to a variety of compounds, of which the most important appears to be 1,25 dihydroxy-vitamin D [1,25-(OH)2D] (DeLuca, 1992). The 1,25(OH)2D is also referred to as calcitriol. Once formed in the kidney, 1,25-(OH)2D is then transported to the intestine, bones or elsewhere in the body, where it is involved in the metabolism of calcium and phosphorus. From studies of vitamin D metabolism, it has been found that the vitamin functions as a hormone. The hormonal form, 1,25-(OH)2D, is the metabolically active form of the vitamin that functions in intestine and bone, whereas 25-(OH)D and vitamin D do not function at these specific sites under physiological conditions (DeLuca, 1992).
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Production of 1,25-(OH)2D is very carefully regulated by parathyroid hormone (PTH) in response to serum calcium and phosphate (PO43-) concentrations. Under conditions of calcium stress, PTH activates renal mitochondrial 1 alpha-hydroxylases, which convert 25-OHD to 1,25-(OH)2D, and inactivates renal and extrarenal 24- and 23-hydroxylases, which convert the 25-OHD [and any 1,25-(OH)2D formed] to inactive metabolites (Goff et al., 1991b). Under conditions with little calcium stress (when little PTH is secreted), the 1 alpha-hydroxylase can also be stimulated by low blood calcium or phosphorus concentration directly. High plasma 1,25-(OH)2D concentration has an inhibitory effect on renal 1 alpha-hydroxylase and a stimulatory effect on tissue 24- and 23-hydroxylases (Engstrom et al., 1987). Thus, production and catabolism of the hormone 1,25-(OH)2D are tightly regulated. It is now known that the most important point of regulation of the vitamin D endocrine system occurs through stringent control of the activity of the renal 1 alpha-hydroxylase. In this way, the production of the hormone 1,25-(OH)2D3 can be modulated according to the calcium needs of the organism (Collins and Norman, 1991).
For most mammals, vitamin D, 25-OHD, and possibly 24,25-(OH)2D3 and 1,25-(OH)2D are all transported on the same protein, called transcalciferin, or vitamin D-binding protein (DBP). In contrast to aquatic species, which store significant amounts of vitamin D in the liver, land animals, do not store appreciable amounts of the vitamin. The body has some ability to store vitamin D, although to a much lesser extent than vitamin A. Principal stores of vitamin D occur in blood and liver, but it is also found in lungs, kidneys and elsewhere in the body. During times of deprivation, vitamin D in these tissues is released slowly, thus meeting vitamin D needs of the animal over a longer period of time (Collins and Norman, 1991). Excretion of absorbed vitamin D and its metabolites occurs primarily in feces with the aid of bile salts.
For mammals, 1,25-(OH)2D is a critical factor in the maintenance of sufficient maternal calcium for transport to the fetus and may play a role in normal skeletal development of the neonate (Lester, 1986). A liberal intake of vitamin D during gestation does provide a sufficient store in newborns to help prevent early rickets. For example, newborn lambs can be provided enough to meet their needs for six weeks. Parenteral cholecalciferol treatment of sows before parturition proved an effective means of supplementing young piglets with cholecalciferol (via the sow's milk) and its more polar metabolites via placental transport (Goff et al., 1984).
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