Vitamin from hepatic retinyl esters

After uptake of the chylomicron retinyl esters, hydrolysis and reesterification occur in the liver. The resulting retinyl esters (predominantly retinyl palmitate) are stored in the liver and can be mobilized as needed in a highly regulated process. Vitamin A mobilization from hepatic retinyl ester stores takes place as the free alcohol retinol bound to a specific plasma transport protein retinolbinding protein (RBP). 

In one study, Tomassi and Olson (1983) examined the effects of dietary fatty acid composition on hepatic retinyl ester composition and on yitamin A utilization in the rat. The fatty acid composition of retinyl esters in the liver was not perturbed by the presence of a large amount of polyunsaturated fat in the diet over a 10-day feeding period. The predominant retinyl ester in the liver was retinyl palmitate, regardless of whether rats were fed 10% com oil, coconut oil, or linseed oil. In addition, the ingestion of polyunsaturated fat did not significantly influence the mobilization rate of vitamin A from the liver. 

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. 

Studies in vitamin A replete animals suggest that most of the retinol is transferred from hepatocytes to the perisinusoidal stellate cells of the liver. Here, it is again esterified by LRAT to form mainly retinyl palmitate (76% to 80%), with smaller amounts of stearate (9% to 12%), oleate (5% to 7%), and linoleate (3% to 4%). The stellate cells contain 90% to 95% of hepatic vitamin A, as cytoplasmic lipid droplets that consist of between 12% to 65% retinyl esters (Batres and Olson, 1987). Studies with [ C]retinyl palmitate show that much of the recently ingested retinol appears more or less immediately in the... 

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. 

More than 90% of the body s supply of vitamin A is stored in the liver. The hepatic parenchymal cells are involved in its uptake, storage, and metabolism. Retinyl esters are transferred to hepatic fat-storing cells (also called Ito cells or lipocytes) from the parenchymal cells. The capacity of these fat-storing cells may determine when vitamin A toxicosis becomes symptomatic. During the development of hepatic fibrosis (e.g., in alcoholic liver disease), vitamin A stores in Ito cells disappear and the cells differentiate to myofibroblasts. These cells appear to be the ones responsible for the increased collagen synthesis seen in fibrotic and cirrhotic livers. 

Zinc deficiency accompanied by a depression in plasma retinol has been noted in several studies. Some investigators have reported an increased liver vitamin A in several species of zinc-deficient animals (Stevenson and Earle, 1956 Saraswat and Arora, 1972 J. C. Smith et aL, 1973, 1976 Brown et aL, 1976 Jacobs et al., 1978 Carney et aL, 1976). There are also reports in humans in an association between lowered zinc, retinol, and RBP (Jacobs et a/., 1978 Solomons and Russell, 1980). J. C. Smith et al, (1973) suggested that hepatic mobilization of vitamin A was impaired by zinc deficiency and their follow-up studies demonstrated a depression in liver and plasma RBP in the zinc-deficient rat compared to pair-fed controls (Brown et al., 1976 Smith et al., 1974). The depression was hypothesized to be the result of a depressed synthesis rather than an increased turnover of RBP. That preformed RBP is present in zinc-deficient rats was demonstrated by Carney et al. (1976) using labeled vitamin A. Zinc-deficient rats, whether or not they were also vitamin A-deficient, were able to mobilize over a short time span a small oral dose of vitamin A as well as could their pair-fed controls. Those animals deficient only in zinc excreted metabolites of the labeled vitamin in a similar quantitative manner as the pair-fed controls for 6 days postdosing. These data suggest that the release of retinol from retinyl ester stores, as well as a depressed RBP synthetic rate, contributed to low plasma levels of vitamin A in zinc deficiency. 

Theoretically, when blood and liver levels of vitamin A are reduced as in alcoholic hepatitis and alcoholic cirrhosis, subjects should receive supplemental vitamin A. Such supplementation, as high as 3000-10,(X)0 xg daily, has been shown to correct abnormal dark adaptation in some alcoholic cirrhotics uncomplicated by zinc deficiency (Morrison et aL, 1978 Russell et aL, 1978 Mobarhan et aL, 1981). Some studies in rats, however, indicate that acute and chronic administration of ethanol impairs hepatic and/or peripheral tissue uptake of newly ingested retinyl ester and/or causes the release of retinyl esters from hepatic tissue... 

Hydrolysis of retinyl esters occurs in the liver both during the hepatic uptake of dietary vitamin A and during the mobilization of retinol from its stores in the liver. The hydrolysis of chylomicron retinyl esters that occurs during hepatic uptake has been discussed above. In addition, retinyl ester hydrolysis must precede the mobilization of retinol from hepatic stores of retinyl ester since retinol is mobilized in the form of the unesterified alcohol (retinol) bound to RBP. Accordingly, it is clear that the enzymatic hydrolysis of retinyl esters in liver represents an important process in the overall metabolism of retinol in the body. 

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