Vitamin differentiation, role

In many cases the relatively complex nature of lipid-based formulations in terms of lipid class, chain length, degree of dispersion, and choice of surfactant makes explanation of the mechanistic information difficult. For example, the bioavailability of vitamin E after administration of vitamin E acetate is greater after administration in a medium-chain triglyceride (MCT)-based emulsion compared with a long-chain triglyceride (LCT)-based lipid solution however, the differential roles of lipid dispersion or lipid class (MCT vs. LCT) cannot be separated [37],... 

Dihydroxyvitamin (283) is the endogenous ligand for the vitamin receptor (VDR). It modulates genomic function in a tissue and developmentaHy specific manner and affects ceU proliferation, differentiation, and mineral homeostasis (74). Vitamin mobilizes calcium from the bone to maintain plasma Ca " levels. Vitamin and VDR are present in the CNS where they may play a role in regulating Ca " homeostasis. Vitamin D has potent immunomodulatory activity in vivo. 

The specific role of vitamin A in tissue differentiation has been an active area of research. The current thinking, developed in 1979, involves initial dehvery of retinol by holo-B >V (retinol-binding protein) to the cell cytosol (66). Retinol is then ultimately oxidized to retinoic acid and binds to a specific cellular retinoid-binding protein and is transported to the nucleus. Retinoic acid is then transferred to a nuclear retinoic acid receptor (RAR), which enhances the expression of a specific region of the genome. Transcription occurs and new proteins appear during the retinoic acid-induced differentiation of cells (56). 

Vitamin A is essential throughout life, including foetal development, but perhaps its most well researched role is that in vision where 11 -cis retinaldehyde is the initial part of the photoreceptor complex in rods and cones. Retinoic acid induces differentiation in epithelial cells and deficiency leads to... 

Retinoids play a role in the regulation of differentiation and development. This they achieve by binding to retinoid receptor-proteins in the nucleus and inhibiting the expression of transcription factors that regulate proliferation. Hence, deficiency of vitamin A can result in impaired differentiation and hence foetal malformation and spon-... 

Vitamin A is essential for growth and development of cells and tissues. In its active form, retinoic acid (RA), it controls the regular differentiation as a ligand for retinoic acid receptors (RAR, RXR) and is involved in the integration (gap junction formation) of cell formations (Biesalski, 1996 Biesalski et al, 1999). Vitamin A plays a substantial role, especially in the respiratory epithelium and the lung. During moderate vitamin A deficiency, the incidence for diseases of the respiratory tract is considerably increased and repeated respiratory infections can be influenced therapeutically by a moderate vitamin A supplementation (Biesalski et ah, 2001 Greenberg et ah, 1997 John et ah, 1997). 

Vitamin D3 is transported to liver where it undergoes a hydroxylation at C-25 into 1a,25-dihydroxyvitamin D3 (calcitriol) (Fig. 64). In the kidney, it undergoes further hydroxylations at different sites, depending on the serum Ca + concentration. The most biologically active metabolite of vitamin D3 is calcitriol, which plays important roles in the regulation of calcium and phosphorus metabolism. It is used for treating bone diseases, but is also involved in the cell proliferation and the inducement of cell differentiation [151]. 

Altered vitamin A homeostasis, primarily manifested as decreased hepatic storage of vitamin A, is another established effect of PBBs in animals. Vitamin A is essential for normal growth and cell differentiation, particularly differentiation of epithelial cells, and some PBB-induced epithelial lesions resemble those produced by vitamin A deficiency. Because it is the primary storage site for vitamin A, the liver has a major role in retinol metabolism. Esterification of dietary vitamin A, hydrolysis of stored vitamin A, mobilization and release into the blood of vitamin A bound to retinol-binding protein, and much of the synthesis of retinol-binding protein occurs in the liver. 

Vitamin A, as retinal, has a clearly established role in vision (Chapter 23) and apparently has a specialized function in reproduction. In vitamin A deficiency no sperm cells are formed in males, and fetal resorption occurs in females. Rats deprived of vitamin Abut fed retinoic acid become blind and sterile but otherwise appear healthy.e bb Evidently either the alcohol or the aldehyde has an essential function in reproduction, whereas bone growth and maintenance of mucous secretions requires only retinoic acid. Indeed, retinoic acid is 100 to 1000 times more active than other forms of vitamin A in these differentiation functions.1 ... 

Vitamin D is also known to have other physiological functions, including a role in immune suppression, hormone secretion, and the differentiation of both normal and malignant cells. 

It is widely accepted that retinoids inhibit tumor growth and development, or the promotional phase of tumorigenesis (1J5) since it is well known that vitamin A plays a marked, as yet ill-defined, role in controlling the growth and differentiation of epidermis and epidermally-derived structures (16-18). Experimental evidence for this hypothesis rests primarily on the observation that conditions of hypervitaminosis A significantly inhibit tumor production even when initiated after application of the carcinogenic insult. Thus, 13-cis-retinoic acid inhibits the induction of transitional cell... 

Writing contemporaneously, Wolf De Luca said42 There is now, we believe, general agreement that vitamin A is to be regarded as a hormone rather than a vitamin in the classical sense of a conenzyme. By hormone we mean a substance secreted into the blood stream which influences tissues and organs so as to differentiate and elaborate new cell types and new enzymes. While the retinoids of vision are secreted into the blood stream in support of the above roles, those destined for use in the visual process are transported in a more sophisticated manner that isolates them from the blood stream. 

In addition to the organs responsible for the development and maintenance of the fetus and newborn, l,25(OH)2D3 receptors have also been localized in several organs from the reproductive apparatus such as the uterus [71], ovary [72] and testis [73]. Since these tissues are not directly associated with calcium translocations, the presence of l,25(OH)2D3 receptors may be related to a role of the hormone in cellular proliferation, differentiation and/or maturation. Accordingly, the levels of testicular l,25(OH)2D3 receptors have been found to correlate with the meiotic and mitotic development of the spermatogonia [73], Clearly, more studies are needed in this area to clarify the role of the vitamin D hormone in these tissues. However,... 

Steatorrhea, the clinical result of insufficient intraluminal lipid hydrolysis, is the most important digestive malfunction in pancreatic exocrine insufficiency. As a rule, concomitant malabsorption of the lipid-soluble vitamins A, D, E, and K must be suspected in these patients. Naturally, potential differential diagnoses have to be considered in patients who present with steatorrhea (Table 26-1). The pivotal role of fat malabsorption in chronic pancreatitis is due to several interacting mechanisms ... 

Obeid, L.M., Linardic, C.M., Karolak, L.A., and Hannun, Y.A., 1993, Programmed cell death induced by ceramide, Science 259 1769-1771 Okazaki, T., Bell, R.M., and Hannun, Y.A., 1989, Sphingomyelin turnover induced by vitamin D3 in HL-60 cells. Role in cell differentiation. J. Biol. Chem. 264 19076-19080 Okazaki, T., Bielawska, A., Bell, R.M., and Hannun, Y. A., 1990, Role of ceramide as a lipid mediator of la, 25-dihydroxyvitamin D3-induced HL-60 cell differentiation. J. Biol. Chem. 265 15823-15831... 

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