Vitamin nuclear binding protein

Hoshi K, Nomura K, Sano Y, and KoshiharaY (1999) Nuclear vitamin K2 binding protein in human osteoblasts homologue to glyceraJdehyde-3-phosphate dehydrogenase. Biochemical Pharmacology S3,1631-8. 

Jiang, H., Xiong, D. H., Guo, Y. F., et al. 2007. Association analysis of vitamin D-binding protein gene polymorphisms with variations of obesity-related traits in Caucasian nuclear families. Int J Obes (Land), 31 1319-24. 

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). 

The overall metabolism of vitamin A in the body is regulated by esterases. Dietary retinyl esters are hydrolyzed enzymatically in the intestinal lumen, and free retinol enters the enterocyte, where it is re-esterified. The resulting esters are then packed into chylomicrons delivered via the lymphatic system to the liver, where they are again hydrolyzed and re-esterified for storage. Prior to mobilization from the liver, the retinyl esters are hydrolyzed, and free retinol is complexed with the retinol-binding protein for secretion from the liver [101]. Different esterases are involved in this sequence. Hydrolysis of dietary retinyl esters in the lumen is catalyzed by pancreatic sterol esterase (steryl-ester acylhydrolase, cholesterol esterase, EC 3.1.1.13) [102], A bile salt independent retinyl-palmitate esterase (EC 3.1.1.21) located in the liver cell plasma hydrolyzes retinyl esters delivered to the liver by chylomicrons. Another neutral retinyl ester hydrolase has been found in the nuclear and cytosolic fractions of liver homogenates. This enzyme is stimulated by bile salts and has properties nearly identical to those observed for... 

Vitamin D is obtained in the diet or by photolysis of 7-dehydrocholesterol in skin exposed to sunlight. Calcitriol works in concert with parathyroid hormone in Ca2+ homeostasis, regulating [Ca2+] in the blood and the balance between Ca2+ deposition and Ca2+ mobilization from bone. Acting through nuclear receptors, calcitriol activates the synthesis of an intestinal Ca2+-binding protein essential for uptake of dietary Ca2+. Inadequate dietary vitamin D or defects in the biosynthesis of calcitriol result in serious diseases such as rickets, in which bones are weak and malformed (see Fig. 10-20b). 

Vitamin A absorbs UV light between 300 and 350 nm. After acute exposure to UVA or UVB a dose-dependent decrease of vitamin A was shown in mouse59 and humans.84 UV irradiation markedly reduced mRNA and protein of the nuclear retinoid receptors RARy and RXRa in humans and led to a near loss of retinoic acid induction of the RAR/RXR target genes and the cellular retinoic acid binding protein II thus effectively causing additionally a functional vitamin A deficiency.85... 

Calcitriol acts like a steroid hormone, binding to, and activating, nuclear receptors that modulate gene expression. More than 50 genes are known to be regulated by calcitriol (see Table 3.3), but vitamin D response elements have only been identified in a relatively small number, including calcidiol 1-hydroxylase and 24-hydroxylase calbindin, a calcium binding protein in the... 

Vitamin D Vitamin D3, a secosteroid (a steroid in which one of the rings has been opened) formed by the action of UV light on 7-dehydrocholesterol. The active form of vitamin D is the hormone 1,25-dihydroxycholecalciferol (calcitriol), formed in the kidney in response to eievated PTH ieveis. It binds to nuclear receptors in intestine, bone, and kidney to activate the expression of calcium-binding proteins. 

How the above described vitamins influence in vitro 3H-tryptophan nuclear receptor binding is not clear. Based upon the experiments with added dithiothreitol, it appears that some vitamins act on the sulfhydryl groups of the receptor, which become modified, which interferes with 3H-tryptophan binding. Reviews of reports by others indicate that certain vitamins can bind to hepatic nuclei. Examples include (1) 3H-a-tocopherol, which has been reported to become incorporated into isolated rat liver nuclei in a nonspecific manner by binding to chromatin nonhistone chromosomal protein,196 and (2) rat liver nuclei, which contain receptors for a folate-binding protein.197 As yet, it is not known whether others act similarly or not. Thus, whether competitive binding to nuclei between vitamins and tryptophan occurs is not known. 

The retinoids comprise a family of polyisoprenoid lipids that inclndes vitamin A (retinol) and stracturaUy related componnds. The biological activity of retinoids can be mod-ihed, for example, by changes in the molecules state of oxidation and cis/trans isomerization. Their activity is also dependent on the levels of specific types of retinoid-binding proteins that exist in extracellular, cytosolic, and nuclear compartments. The role of retinoids in gene expression represents an important biological function for this family of molecules. Retinoid-dependent modulation of gene expression is critical for normal cell and tissue function in mature as well as developing animals. 

The next stage involves the synthesis of specific calcium-binding proteins, typified by the intestinal CaBP discussed in Section 62.1.3.4.5, which probably stimulates the transport of calcium. The role of the protein in vitamin D-dependent absorption of calcium is supported by the good correlation between the concentration of CaBP and the rate of calcium absorption. Under conditions of low calcium or phosphorus diets, chicks and other animals produce more intestinal CaBP to increase the efficiency of uptake of calcium. In general, adaptation to a low calcium diet involves increased synthesis of l,25-(OH)2D3 and the intestinal CaBP. Lowered requirements for calcium in old age are manifested by lower levels of both factors. Advances have been made in the localization of the cellular sites of l,25-(OH)2D3 in target tissue. Receptor proteins have been extracted, and, in the case of the chick intestinal receptor, purified to homogeneity." The ability of l,25-(OH)2D3 to stimulate absorption of calcium is blocked reversibly by inhibitors of RNA and protein synthesis. This suggests that l,25-(OH)2D3 functions by a nuclear mechanism. 

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