Vitamin bone structure

Vitamin D plays a very central role in maintaining the integrity of bone structure. The vitamin actually comprises a set of closely related derivatives of cholesterol that incorporate a 5,7 diene in ring B. The compounds are not actually active per se, requiring activation by ultraviolet light. In a typical example the action of light on... 

Several synthetic vitamin D analogs have been prepared and their activities investigated. Of particular importance for potential anti-cancer and immune supression drugs, are vitamin D compounds whose bone calcium activity is low and cell differentiation activity is high. Compound 1 and 2 are traditional vitamin D structures with high bone calcemic activity (calcium homeostasis) and only modest cell differentiation activity. 

The body s storehouse of calcium is bone tissue. When the supply of calcium from external sources, the diet, is insufficient, the body uses a mechanism to compensate for this shortage. With vitamin D in a critical role, this mechanism removes calcium from bone to enable other functions to continue to take place. It is evident then that prolonged dietary calcium deficiency can weaken the bone structure. Unfortunately, current studies show that as many as 75% of the American population may not be consuming sufficient amounts of calcium. Develop-... 

Glu (first 40 residues from the N-terminus) of certain proteins involved in blood clotting and bone structure, is carboxylated to y-carboxyglntamate (Gla) by the vitamin K-depend-ent carboxylase. Gla is invariably involved in Ca -binding. Hydroxylation of P and K occurs in procollagen in which P of —X-P-G— is y-hydroxylated and K in —X-K-G— is 8-hydroxylated. These hydroxylalions are essential to the maturation of collagen in the formation of triple helix (y-OH-Pro) and cross-linkages (8-OH-Lys). 

Combined treatment with isotretinoin and vitamin A may result in a condition similar to overdosage with vitamin A. Concurrent use should therefore be avoided or very closely monitored because changes in bone structure can occur, including premature fusion ofthe epiphyseal discs in children. ... 

Other reports describe patients whose response to usual doses of vitamin D was poor, because of concurrent anticonvulsant treatment with pheny-toin and phenobarbital or primidone. " Other reports clearly show low serum calcium levels,low serum vitamin D levels, osteomalacia, and bone structure alterations in the presence of phenytoin. 

Collagen cross-links. The quality of collagen cross-links in the bone structure is closely associated with bone strength. A formation of such impaired crosslinks is accelerated by vitamin Bg deficiency and excessive oxidative stress. 

Because of the possibility of its biosynthesis in the body and its biological function (it is an antirachitic vitamin connected with the metabolism of calcium and phosphorus, which are necessary for growth, development and maintenance of bone structure), some reports state that vitamin Dj is more a hormone than a vitamin. 

A disease of calcium metabolism in which there are changes ir bone structure associated with chronic renal failure. A factor in the aetiology of the condition may be the failure to hydroxylate vitamin D by the kidney. The disease may be treated by giving large doses of vitamin D. 

Little is known about the biochemical mechanism of vitamin D action. It promotes the absorption of Ca++-ions in the gastro-intestinal tract and influences the metabolism of bone tissue. Deficiency of vitamin D results in the clinical syndrome rachitis (also in animal experiments), characterized by a softenii (inadequate calcification) of the bones. Excessive administration of vitamin D produces a hyper-vitaminosis, during which calcium is again mobilized out of the bone structure this hypervitaminosis resembles the action of the parathyroid hormone. 

Lead has a high affinity for bone, partly due to its antagonistic relationship with calcium. The greatest amount of lead in the body is the skeleton, which acts as a reservoir for lead. The influence of lead upon bone must be considered from the perspective of vitamin the metabolism of which is significantly altered in lead toxicity. Bone structure is in a constant state of self-renewal, with continual controlled destruction, reduction, and rebuilding. Lead is known to influence the various biochemical and physiological events involved with this process. 

Isolation and Structure Determination. The isolation and stmcture elucidation of vitamin D are closely related to the efforts to understand and cure tickets and related bone diseases. The advent of the use of soft coal, the migra tion of people to cities, and the tendency of people and animals to spend less time in sunshine caused a decline in the abiUty of populations to synthesize sufficient quantities of vitamin D. This led to the increased incidence of tickets, beginning around the mid-1600s (3). 

Antioxidants in fruits and vegetables including vitamin C and (3-carotene reduce oxidative stress on bone mineral density, in addition to the potential role of some nutrients such as vitamin C and vitamin K that can promote bone cell and structural formation (Lanham-New 2006). Many fruits and vegetables are rich in potassium citrate and generate basic metabolites to help buffer acids and thereby may offset the need for bone dissolution and potentially preserve bone. Potassium intake was significantly and linearly associated with markers of bone turnover and femoral bone mineral density (Macdonald and others 2005). 

Vitamin C is essential for the formation of collagen, the principal structural protein in skin, bone, tendons, and ligaments, being a cofactor in the hydroxylation of the amino acids proline to 4-hydroxyproline, and of lysine to 5-hydroxylysine. These hydroxyamino acids account for up to 25% of the collagen structure. Vitamin C is also associated with some other hydroxylation reactions, e.g. the hydroxylation of tyrosine to dopa (dihydroxyphenylalanine) in the pathway to catecholamines (see Box 15.3). Deficiency leads to scurvy, a condition characterized by muscular pain, skin lesions, fragile blood vessels, bleeding gums, and tooth loss. Vitamin C also has valuable antioxidant properties (see Box 9.2), and these are exploited commercially in the food industries. 

The acoustic micrograph in Fig. 1.5(a) came from a 5-week-old preparation. It was fixed in alcohol, and stained for alkaline phosphatase and, with von Kossa stain, for biomineral material. The biomineral material of interest here is hydroxyapatite, the principal crystalline mineral constituent of bone. The ordered structure visible within the matrix is not seen with either the light or electron microscopes. But the acoustic microscope can also work perfectly well with unfixed, unstained specimens. Figure 1.5(b) is an acoustic micrograph of matrix and cells from a 17-year-old male. In addition to the standard ingredients of culture medium, these cells were specifically stimulated with beta-glycerolphosphate and a vitamin C preparation. Because the acoustic... 

Vitamin D deficiency leads to defects in the structure of bones, a disease known as rickets , common in miners who lived and worked underground during the daytime. They did not have the normal share of sunlight, but it took some time to realize that the lack of vitamin D was related to a photochemical reaction. This reaction is shown in Figure 5.23 in a simplified form, in order to point out the important electrocyclic process. 

The controlled deposition of calcium salts is essential for the development of extracellular structures such as bones, teeth and shell. The process begins with uptake of calcium in the intestine, followed by transport, and then the laying down of structures. A complex system is necessary for the control of all these stages, and involves, for example, vitamin D, parathyroid hormone, calcium-binding proteins for transport, and a range of other proteins and polysaccharides for ordered deposition. Precipitation of calcium salts in the incorrect location can result in stone formation, osteoarthritis, cataracts and arterial disorders. 

Deficiency syndromes of Zn, Cu, Cr, Se and Mo have occurred in patients on total parenteral nutrition (TPN). There is still much research to be done in assessing the nutritional status of many elements and understanding their metabolism, so that normal dietary intake may be supplemented for health benefits. Table 2 is a summary of the amounts required, the functions and the nutritional (usually dietary) imbalances in humans, where known, of the essential trace elements.31-33 (Note that this summary does not attempt to include imbalances related to environmental toxicology and occupational hazards.) Several trace elements have important functions in the immune system. Some are associated with nucleic acid. Others have structural roles, such as Si in cartilage, F and Zn in bone. They may be parts of vitamins, such as Co in vitamin B12, or hormones, such as iodine in thyroid hormones, Zn and Cr have a role in the synthesis and action of insulin.31-33... 

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