Retinol-binding protein vitamin

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 first example is the plasma-borne retinol-binding protein, RBP, which is a single polypeptide chain of 182 amino acid residues. This protein is responsible for transporting the lipid alcohol vitamin A (retinol) from its storage site in the liver to the various vitamin-A-dependent tissues. It is a disposable package in the sense that each RBP molecule transports only a single retinol molecule and is then degraded. 

Figure S.3 Schematic diagram of the structure of human plasma retinol-binding protein (RBP), which is an up-and-down P barrel. The eight antiparallel P strands twist and curl such that the structure can also be regarded as two p sheets (green and blue) packed against each other. Some of the twisted p strands (red) participate in both P sheets. A retinol molecule, vitamin A (yellow), is bound inside the barrel, between the two P sheets, such that its only hydrophilic part (an OH tail) is at the surface of the molecule. The topological diagram of this stmcture is the same as that in Figure 5.2. (Courtesy of Alwyn Jones, Uppsala, Sweden.)...

Honkanen, R.D., Kontinnen, Y.T. and Mussalo-Rauhamaa, H. (1989). Vitamins A and E, retinol binding protein and zinc in rheumatoid arthritis. Clin. Exp. Rheum. 7, 465-469. 

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... 

Retinol-binding protein is crucial for binding vitamin A in the serum. 

Retinol-binding protein Vitamin D-binding protein... 

K2. Kanai, M., Raz, A., and Goodman, D. S., Retinol-binding protein the transport protein for vitamin A in human plasma. J. Clin. Invest. 47, 2025-2044 (1968). 

Blaner, W. S. (1989). Retinol-binding protein The serum transport protein for vitamin. Endocrinol. Rev. 10,308-316. 

In the body retinol can also be made from the vitamin precursor carotene. Vegetables like carrots, broccoli, spinach and sweet potatoes are rich sources of carotene. Conversion to retinol can take place in the intestine after which retinyl esters are formed by esterifying retinol to long chain fats. These are then absorbed into chylomicrons. Some of the absorbed vitamin A is transported by chylomicrons to extra-hepatic tissues but most goes to the liver where the vitamin is stored as retinyl palmitate in stellate cells. Vitamin A is released from the liver coupled to the retinol-binding protein in plasma. 

Retinol (vitamin A) is found in foods of mammalian origin in the form of retinyl ester, or in fruits and vegetables as carotenoids with provitamin A activity, especially P-carotene (provitamin A). In enterocytes, retinol binds to cellular retinol-binding protein type II (CRBPII), which directs the esterification by the enzyme lecithin retinol acyltransferase (LRAT). 

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. 

Absorption, transport, and storage of vitamin A and its derivatives. RBP = retinol-binding protein. 

Figure 4.13 Anatomy of selected proteins. (A) The /3 subunit of hemoglobin carrying a heme molecule (B) triose isomerase and (C) /3-lactoglobulin carrying a molecule of vitamin A. Spirals represent helix segments, and the broad arrows are pleated sheet polypeptide segments showing the direction from the N to the C terminus. (A and B reproduced with permission from Richardson JS. The anatomy and taxonomy of protein structure. Adv Prot Chem 34 168-339, 1981. C reproduced with permission from Papiz MZ, Sawyer L, Eliopoulos EE, North ACT, Findlay JBC, Sivaprasadarao R, Jones TA, Newcomer ME, Kraulis PJ. The structure of beta-lactoglobulin and its similarity to plasma retinol-binding protein. Nature 324 383-385, 1986.)...

In the intestinal mucosal cells, /3-carotene is cleaved via an oxygenase (an enzyme that introduces molecular 02 into organic compounds) to frans-retinal (aldehyde form of trans-retinol, as shown in Table 6.2), which in turn is reduced to frans-retinol, vitamin Av Retinol is then esterified with a fatty acid, becomes incorporated into chylomicrons, and eventually enters the liver, where it is stored in the ester form until it is required elsewhere in the organism. The ester is then hydrolyzed, and vitamin Ax is transported to its target tissue bound to retinol-binding protein (RBP). Since RBP has a molecular weight of only 20,000 and would be easily cleared by the kidneys, it is associated in the bloodstream with another plasma protein, prealbumin. 

The ultimate dependence of vitamin E for transport by liver and intestinal cells via apoB lipoproteins may explain the severe vitamin E deficiency observed in ABL. In contrast, apoB lipoprotein assembly is required only for the mobilization of dietary vitamin A by the intestinal cells liver distributes the endogenous vitamin A to other tissues by retinol-binding protein. Unlike vitamins E and A, dietary vitamin K may only partially depend on apoB lipoproteins for its transport across the intestinal epithelial cells and tissue targeting and may explain why bleeding diathesis is rarely observed in ABL. 

When vitamin A stores are adequate, the liver secretes retinol bound to retinol-binding protein (RBP) into the circulation to provide tissues with a constant supply of vitamin A. In the circulation, the retinol-RBP complex is found bound to another circulating protein of hepatic origin, transthyretin (TTR). TTR also binds thyroid hormone and consequently plays a role in the transport of both vitamin A and thyroid hormone. The molecular size of the retinol-RBP complex is quite small, and the formation of the... 

Retinol is released from the liver bound to an a-globulin, retinol binding protein (RBP) this serves to maintain the vitamin in aqueous solution, protects it against oxidation, and also delivers the vitamin to target tissues. RBP binds 1 mol of retinol per mol of protein. 

Plasma Retinol Binding Protein Measurement of plasma concentrations of RBP may give some additional information. Indeed, it has been suggested that because retinol is susceptible to oxidation on storage of blood samples, measurement of RBP may be a better indication of the state of vitamin A status. In adequately nourished subjects, about 13% of immunologi-caUy reactive RBP in plasma is present as the apo-protein, whereas in vitamin A-deficient children, the proportion of apo-protein may rise to 50% to 90% of... 

Peterson P Nilsson S, Ostbergl, RaskL, and Vahlquist A (1974) Aspects of the metabolism of retinol-binding protein and retinol. Vitamins and Hormones 32,181-214. 

Vitamin A Both vitamin A (= retinol) and A2 (= 3-dehydroreti-nol) occur in nature. Like their derivatives, they are classed under the umbrella term axerophtol. The major provitamin is p-carotin. Vitamin A is stored as a lipoglycoprotein complex in the fat-storing cells of the liver. It is released when necessary by being coupled with a retinol-binding protein (RBP) and is then transported to the cells which require vitamin A. In the case of zinc deficiency the rate of RBP synthesis is markedly increased, and as a result serum retinol concentration is reduced. Retinol deficiency can be compensated by zinc substitution. The daily requirement is approx. 1 mg. (7, 36)... 

Zinc assumes a special role in the intrahepatic formation of retinol-binding protein, which is essential for the release of vitamin A into the blood. Zinc deficiency results in a decrease in RBR Furthermore, as a part of ADH, zinc is crucial for alcohol degradation in the hepatocytes and for enzyme activation in the detoxification of ammonia in the urea cycle, (s. fig. 3.12 )... 

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