Retinol storage

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. 

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... 

Storage. The liver not only stores energy reserves and nutrients for the body, but also certain mineral substances, trace elements, and vitamins, including iron, retinol, and vitamins A, D, K, folic acid, and Bi2. 

Thunberg, T., Ahlborg, U. G., Hakansson, H., Krantz, C., and Monier, M. (1980). Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the hepatic storage of retinol in rats with different dietary supplies of vitamin A (retinol). Arch. Toxicol. 45, 273-285. 

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. 

The leveisal of the oxidative pathway of vitamin A (retinol —r retinal —>-retinoic add) does not occur in the body, When retinoic acid is feci to animals, even in relatively large doses, there is no storage and, in fact, die molecule is rapidly metabolized and cannot be found several hours after administration. The metabolic products have not been fully identified. Several fractions from liver or intestine, isolated after administering retinoic add marked with carbon-14, have been shown to have biological activity. 

The liver of meat animals is a rich source of vitamin A, for this organ is the body s main storage site of the vitamin. Fish liver oils, particularly halibut liver oil, are incredibly rich in the vitamin and are too potent to be consumed as foods. Typical food sources of vitamin A (in /ag retinol equivalents/100 g) are sheep and ox liver, 15,000 butter, 830 cheese, 320 eggs, 140 herring and... 

There are many types of preparations that contain retinol. Absorption is greatest for aqueous preparations, intermediate for emulsions, and slowest for oil solutions. Whereas oil-soluble preparations may lead to greater hepatic storage of the vitamin, water-miscible preparations usually provide higher concentrations in plasma. Vitamin A is available as capsules. Tretinoin (all-trans-retinoic acid Retin A) is available for topical use. Isotretinoin (13-ri.s-retinoic acid Accutane) is available for oral use, as is etretinate (Tegison). 

C32. Comstock, G. W., Alberg, A. J., and Helzlsouer, K. J., Reported effects of long-term freezer storage on concentrations of retinol, beta-carotene, and alpha-tocopherol in serum or plasma summarized. Clin. Chem. 39, 1075-1078 (1993). 

Vitamin A (retinol) is essential for normal growth and cell differentiation, particularly for epithelial cells. 2,3,7,8-TCDD has been shown to decrease the storage of vitamin A in rodents. Decreased ability to store vitamin A (retinol) was found in rats and guinea pigs however, partial recovery of the retinol content by week 16 postexposure was reported only in rats. A single oral dose of 2,3,7,8-TCDD caused a 70% reduction in the liver storage of retinol in rats when measured 2 months postexposure (Thunberg et al. 

Figure 29-3. Chemical structures of important vitamin A species and the provitamin A carotenoid i-carotene. All-fra/w-fi-carolene (T) is the most important provitamin A carotenoid, which can be converted to all-fraws-retinal and then all-tram-retinol (If), which by definition is vitamin A. All-tram-retinol can be esterified with long-chain fatty acids to form retinyl ester (III), the storage form of vitaminA in the body.The active form of vitamin A in vision is 11-cts-retinal (TV).The transcriptionally active forms of vitaminA are all-tram-retinoic acid (V) and 9-cts-retinoic acid (VI). 13-cA-Retinoic acid (VII) has poor transcriptional regulatory activity but is used clinically as isotretinoin to treat skin diseases.

Structurally, vitamin A and many synthetic retinoids consist of a (3-ionone ring, a polyunsaturated polyene chain, and a polar end group. The polar end group can exist in several oxidation states, as retinol, retinal, or retinoic acid. Retinol and retinyl esters are the most abundant vitamin A forms found in the body (Blaner and Olson, 1994). Retinol can be esterified with long-chain fatty acids (mainly palmitate, oleate, and stearate) to form retinyl esters, which are the body s storage form of vitamin A. Retinol also can undergo oxidation to retinal, which can be oxidized further to retinoic acid. The active... 

Liver Storage and Release of Retinol Tissues can take up retinyl esters from chylomicrons, but most is left in the chylomicron remnants that are taken up into the liver by endocytosis. The retinyl esters are hydrolyzed at the hepatocyte cell membrane, and free retinol is transferred to the rough endoplasmic reticulum, where it binds to apo-RBP. Holo-RBP then migrates through the smooth endoplasmic reticulum to the Golgi and is secreted as a 1 1 complex with the thyroid hormone binding protein, transthyretin (Section 2.2.3). 

In most tissues, apo-CRBP does not bind to enzymes only the holo-CRBP binds. However, in the liver, apo-CRBP(I) does bind to LRAT and acts to reduce the rate of esterification of retinol when there is a significant excess of apo-CRBP. This serves to reduce the esterification of retinol for storage at times of low retinol availability and will presumable direct retinol into the endoplasmic reticulum for binding to apo-RBP for export. Apo-CRBP(II) in the intestinal mucosa does not bind to LRAT. 

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... 

An alternative approach to determining requirements is to measure the fractional rate of catabolism of the vitamin by use of a radioactive tracer, then determine the intake that would be required to maintain an appropriate level of liver reserves. As discussed in Section2.2.1.1, when the liver concentration rises above 70 /rmol per kg, there is increased activity of the microsomal oxidation of vitamin A and biliary excretion of retinol metabolites. The fractional catabolic rate is 0.5% per day assuming 50% efficiency of storage of dietary retinol, this gives a mean requirement of 6.7 /rg per kg of body weight and a reference intake of 650 to 700 /rg for adult men (Olson, 1987a). Reference intakes for vitamin A are shown in Table 2.4. 

Blomhoff, R., Holte, K., Naess, L., Beig, T. Newly administered (3 H) retinol is transferred from hepatocytes to stellate cells in bver for storage. Exp. Cell. Res. 1984 150 186-193... 

The uptake of chylomicron remnants by the liver results in delivery of retinol to this organ for storage as a lipid ester within lipocytes. 

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