Liver serum retinol binding protein

Most of the retinol that is delivered to the eye originates in the liver, and is released into the circulation (mainly in the all-trans configuration) bound to an M, 21,000 protein, serum retinol-binding protein (RBP). This protein, which contains no bound lipid or carbohydrate, circulates as a 1 1 complex with transthyretin (TTR, originally prealbumin) (see Chapter 8 for detailed discussion). 

Free retinol is released from the liver as a 1 1 complex of retinol with the 21-kDa retinol-binding protein.k l This protein is normally almost saturated with retinol and is bound to another serum protein, the 127-residue transthyretin (prealburnin).m/n Some of the retinol is oxidized to retinoic acid. 

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)... 

Alcohol may also act indirectly by causing liver disease, which in turn can affect the capacity of the liver to export vitamin A, thereby enhancing its local toxicity. In alco-hoUcs the carrying capacity of retinol binding protein was increased, even in those with low serum retinol concentrations (97). In such cases, caution in the amount of vitamin A used for therapy is recommended. Similarly, diets that are severely deficient in protein can affect the capacity of the liver to export vitamin A and enhance its hepatotoxicity. 

Vitamin A is readily absorbed from the intestine as retinyl esters. Peak serum levels are reached 4 h after ingestion of a therapeutic dose. The vitamin is distributed to the general circulation via the lymph and thoracic ducts. Ninety percent of vitamin A is stored in the liver, from which it is mobilized as the free alcohol, retinol. Ninety-five percent is carried bound to plasma proteins, the retinol-binding protein. Vitamin A undergoes hepatic metabolism as a first-order process. Vitamin A is excreted via the feces and urine. Beta carotene is converted to retinol in the wall of the small intestine. Retinol can be converted into retinoic acid and excreted into the bile and feces. The elimination half-life is 9 h. 

There are also changes in the binding proteins in plasma as a result of the disease process. Since serum albumin falls in association with any acute iUness, this inevitably leads to a fall in plasma zinc concentration. Similarly a reduction in retinol-binding-protein concentration as part of the APR or protein malnutrition also leads to a fall in serum retinol levels, whatever the amount of retinol stores within the liver. 

Prealbumin is the transport protein for thyroxine and a carrier for retinol-binding protein. The body s content of prealbumin is low (10 mg/kg of body weight), and it has a very short biologic half-fife (I to 2 days). Prealbiunin may be reduced in as few as 3 days after calorie and protein intake is significantly decreased, or when hypercatabolism or severe metabolic stress (tramna or bmns) is present. Because of its short half-life, it is most useful in monitoring the shortterm, acute effects of nutrition support. As with ALB and TFN, sermn prealbumin concentrations are depressed in those with liver disease due to decreased hepatic synthesis. Increased serum prealbumin concentrations have been noted in patients with renal disease due to impaired renal excretion. 

Hepatic depletion of vitamin A stores is caused by chronic ethanol consumption (Bonjour, 1981). Night blindness suffered by alcoholics has been attributed to a low intake of vitamin A (McClain et aL, 1979). However, Sato and Lieber (1982) have demonstrated that ethanol depletes hepatic vitamin A stores in baboons and rats even when it is administered in combination with a nutritionally adequate diet. In addition, animals consuming ethanol in marginal diets were depleted more rapidly of vitamin A. No effect of ethanol intake on retinol binding protein or on serum vitamin A levels could be detected in these studies. Leo and Lieber (1982) found that hepatic vitamin A was depleted to one-fifth of normal levels in alcoholics with only moderate liver disease. Sato and Lieber (1982) observed that retinoic acid was more rapidly metabolized by the MFO system after chronic ethanol intake, and they postulated that vitamin A depletion was the result of MFO enzyme induction. 

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