Action of Vitamin

A number of geometric isomers of retinol exist because of the possible cis-trans configurations around the double bonds in the side chain. Fish liver oils contain mixtures of the stereoisomers synthetic retinol is the all-trans isomer. Interconversion between isomers readily takes place in the body. In the visual cycle, the reaction between retinal (vitamin A aldehyde) and opsin to form rhodopsin only occurs with the 11 -cis isomer. 

Ethers and esters derived from the alcohol also show activity in vivo. The ring structure of retinol ((i-ionone), or the more unsaturated ring in 3-dehydroretinol (dehydro-P-ionone), is essential for activity hydrogenation destroys biological activity. Of all known derivatives, all-/ran,v-retinol and its aldehyde, retinal, exhibit the greatest biological potency in vivo 3-dehydroretinol has about 40% of the potency of all-bms-retinol. 

Retinoic acid (vitamin A acid), in which the alcohol group has been oxidized, shares some but not all of the actions of retinol. Retinoic acid is ineffective in restoring visual or reproductive function in certain species in which retinol is effective. Flowever, retinoic acid is very potent in promoting growth and controlling differentiation and maintenance of epithelial tissue in vitamin A-deficient animals. Indeed, all-trans-retinoic acid (tretinoin) appears to be the active form of vitamin A in all tissues except the retina, and is 10- to 100-fold more potent than retinol in various systems in vitro. Isomerization of this compound in the body yields 13-n.v-rctinoic acid (isotretinoin), which is nearly as potent as tretinoin in many of its actions on epithelial tissues but may be as much as fivefold less potent in producing the toxic symptoms of hypervitaminosis A. 

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Boyer, P. D., 1970. The Enzymes, 3rd ed. New York Academic Pre.s.s. A good reference. source for the mechanisms of action of vitamins and coenzymes. 

Blasiak J, Kowalik J. 1999. Effect of paraoxon-methyl and parathion-methyl on DNA in human lymphocytes and protective action of vitamin C. Pestic Sci 55 1182-1186. 

There is evidence from a number of in vitro studies that the vitamin E peroxyl radical formed during fatty-acid degradation may be converted to vitamin E plus nonradical through the actions of vitamin C (Burton et al., 1985). RA patients have reduced serum ascorbate levels (Situnayake et al., 1991) and potentially a reduced capacity for the regeneration of vitamin E. In vitro studies suggest that vitamin E becomes a pro-oxidant when ascorbate levels are low (Bowry and Stocker, 1993). 

Thomas, S.R., and Stocker, R., 2000, Molecular action of vitamin E in lipoprotein oxidation impheations for atherosclerosis. Free Radio. Biol. Med. 28 1795-1805. 

The main action of vitamin E in human tissue is to prevent oxidation of polyunsaturated fatty acids (PUFA), thereby protecting lipid and phospholipids in membranes. Vitamin E interacts syn-ergically with other nutrients, such as vitamin C, selenium, and zinc, which are also involved in the oxidation pathway. The recommended intake is strongly related to the quantity of PUFA consumption. Some studies [454-456] on animal models and epidemiological trials in human suggest... 

Mithramycin (also known as MIT and plicamy-cin) is an antibiotic that binds to DNA to regulate transcription. It attaches to specific regions of DNA that are rich in guanine and cytosine. It appears to lower serum calcium concentrations by blocking the hypercalcemic action of Vitamin D. After IV administration about 25% of the drug is excreted in the urine after 2 hours, and 40% after 15 hours. The main indications are treatment of testicular tumors and control of hypercalcemia and hypercalciuria. 

Mechanism of Action An antibiotic that forms complexes with DNA, inhibiting DNA-directed RNA synthesis. May inhibit parathyroid hormone effect on osteoclasts and inhibit bone resorption. TherapeuticEffect Lowers serum calcium and phosphate levels. Blocks hypercalcemic action of vitamin Dand action of parathyroid hormone. Decreases serum calcium. 

Figure 17.1 The coagulation cascade., Site of action of vitamin K antagonists LMWH, low molecular weight heparin.

The changes in calvarial phosphatase activities observed in animals treated with 25-(OH)D3 are totally different from those obtained with either 1.25-(OH)2D3 or 24.25—(OH)2D3. This fact indicates that physiological doses of 25-(OH)D3 may have an effect on cellular activity, independent of the conversion of this metabolite into these dihydroxyderivatives. The various effects of these vitamin D3 metabolites cannot be correlated with changes in serum calcium and/or phosphate concentrations. Among those factors other than serum calcium and phosphate concentrations that may be involved in the mechanism of action of vitamin D3 metabolites on bone phosphatase activities, the parathyroid hormone is of importance. This hormone is known to be a potent activator of bone phosphatases223,224,228. Parathormone increases the content of alkaline, neutral and acid phosphatases in mouse calvaria in vitro. Calcitonin does not prevent the increase of those enzymes while dichloromethylene diphosphonate causes a decrease in acid phosphatase and pyrophosphatase226. ... 

A total synthesis of vitamin B12 was announced in 1972, as the result of a collaborative effort between R. B. Woodward (Harvard) and A. Eschenmoser (Zurich). The synthesis was completed after 11 years of effort involving 100 co-workers from 19 countries. A number of important techniques and reactions of synthetic value were developed during the course of this work, including the principle of conservation of orbital symmetry (the Woodward-Hoffman rules, Section 21-10). The biochemical action of vitamin B12 is considered in Chapter 31. 

Dolphin, D. (ed.), S12, vols. 1 and 2. New York Wiley-Inter-science, 1982. Chemistry and mechanism of action of vitamin B12. 

To try to give a perspective to current ideas on the mode of action of vitamin E, it might be prudent to examine the development of our knowledge of this vitamin. Its history is littered with fact and myth but for most people it is the vitamin of reproduction. 

To investigate the mode of action of vitamin E and related structures using the colon model, two hypotheses were tested (l)that their antioxidant properties contribute to the response and (2) that the vitamin was acting as an agonist on a receptor with structural requirements for producing activity in hypoxia. Testing the various available tocopherols on the colon model... 

Figure 5.4. Schematic representation of possible sites of action of vitamin E and related chemicals in...

FIGURE 61.5 Actions of vitamin D on calcium metabolism. PTH = parathyroid hormone. 

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