Retinyl esters accumulation

Within the enterocyte, retinol is bound to cellular retinol binding protein (CRBP 11) and is esterified by lecithin retinol acyltransferase (LRAT), which uses phosphatidylcholine as the fatty acid donor, mainly yielding retinyl palmitate, although small amounts of stearate and oleate are also formed. At unphysiologically high levels of retinol, when CRBP 11 is saturated, acyl coenzyme A (CoA) retinol acyltransferase (ARAT) esterifies the free retinol that accumulates in intracellular membranes. Then the retinyl esters enter the lymphatic circulation and then the bloodstream (in chylomicrons), together with dietary lipid and carotenoids (Norum et al., 1986 Olson, 1986 Blomhoff et al., 1991 Green et al., 1993 Harrison and Hussain, 2001). 

The test requires two samples of blood, taken before and 5 hours after the test dose of retinol. A modified RDR test involves giving a test dose of dehydroretinol, then determining the ratio of dehydroretinokretinol in a single plasma sample taken 30 hours later. Again, because of the accumulation of RBP in the liver in deficiency and because in deficiency there is less dilution of dehydroretinol with liver pools of retinyl esters, the ratio is inversely proportional to the liver stores of retinol (Tanumihardjo et al., 1987). 

Finally, an abundant protein in the RPE, RPE65, seems to play a role in the retinoid cycle, but the exact role remains a mystery. Mice lacking this protein accumulate all-trans-retinyl esters that concentrate within lipid droplets in RPE cells (84). These mice are completely devoid of 11-cis-retinal and other cis-retinoid metabolites and are severely com-... 

An extensive study was carried out in rats given excessive vitamin A in doses sufficient to cause both growth disturbances and fatty livers (Mallia et al., 1975). The hypervitaminotic rats showed large increases in serum vitamin A levels, which were mainly due to elevations in the circulating levels of retinyl esters, and decreased levels of serum RBP. In these toxic rats, most of the serum vitamin A and virtually all of the retinyl esters were found in association with the serum lipoproteins of hydrated density < 1.21. It was concluded that the serum lipoproteins play an important role in the transport of the vitamin A that accumulates in the serum in hypervitaminosis A. It was also suggested that serum lipoproteins may nonspecifically deliver vitamin A to biological membranes and, hence, lead to vitamin A toxicity. 

In rats and frogs exposed to high levels of illumination, retinoid passes from the retina to the RPE it accumulates in the RPE in the form of all-rran -retinyl esters. In the case of the frog, these are found in the oil droplets (Fig. 10). The end result is therefore similar to that observed when retinol is delivered to die... 

The retinoid stored in the RPE from these eyes was predominantly retinyl ester. No accumulation of free retinol was observed. As in normal eyes (Bridges et al., 1982), the esters consisted mainly of palmitate with a smaller proportion of stearate. The rate of esteriHcation of aIl-rran5-[ H]retinol was measured in RPE homogenates and was not considered to be significantly lower than normals. 

Overall, the body is efficient at conserving retinol, but relatively inefficient in degrading and eliminating excess retinoids. These differences seem to explain the propensity for retinyl esters to accumulate in tissues when vitamin A is consumed in amounts that substantially exceed requirements. 

Adults require a maintenance level of vitamin A. The RDA is based on maintaining an adequate level of vitamin A in liver while meeting normal tissue demands. In animals fed a normal vitamin A adequate diet, retinyl esters tend to accumulate as the animal ages, such that it becomes very difficult to induce vitamin A deficiency in adult animals, even by feeding them a diet free of vitamin A. These data imply that tissue reserves readily make up for lapses in the day-to-day intake of vitamin A. As is evident from Table 1, some foods contain an amount of vitamin A well in excess of 100% of the daily value (%DV). 

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