Retinyl esters hydrolysis

Wei S, Lai K, Patel S, Piantedosi R, Shen H, Colantuoni V, Kraemer FB, and Blaner WS (1997) Retinyl ester hydrolysis and retinol efflux from BFC-lbeta adipocytes. Journal... 

The isomerization reaction to 11-cis-reti-nol likely occurs through one of two possible mechanisms. First, the all-trans-retinyl ester may be a substrate for an as yet identified "isomerohydrolase"that uses the free energy of retinyl ester hydrolysis to drive the isomerization reaction (22). In this case, the product of the reaction, 11-cis-retinol, would be generated in essentially one step by a single enzyme. 

HJvitamin A-labeled chylomicrons, values for only 3 of the 24 fractional transfer coefficients had to differ to fit the two data sets. Thus we speculate that these three parameters [L(5,6), L(3,4), and L(22,5) Fig. 6] are sensitive to vitamin A status. This makes physiological sense since these parameters reflect retinyl ester hydrolysis and stellate cell retinol secretion. 

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). 

Dietary retinyl esters, retinol, and provitamin A carotenoids are dispersed and emulsified in the stomach during the gastric phase of lipid digestion. They then enter the lumen of the duodenum where extensive hydrolysis of retinyl esters takes place. In infants, the bile salt-stimulated lipase in human milk may play a role in retinyl ester hydrolysis in the duodenum (Fredrikzon et al., 1978). The major retinyl ester hydrolase activity that acts in the intestines is, however, derived from the pancreas. 

The pancreatic enzyme mainly responsible for retinyl ester hydrolysis appears to be the same enzyme that catalyzes intraluminal cholesteryl ester hydrolysis (Erlanson and Boigstibm, 1968 Lombardo and Guy, 1980). This enzyme has been purified from rat (Calame et al.. 1975) and from porcine (Momsen and Brockman, 1977) pancreas, and from human pancreatic juice (Lombardo et al.. 1979). The enzyme appears to be a relatively nonspecific carboxylic ester hydrolase that can act on a wide variety of esters as substrates. Thus the purified human enzyme hydrolyzes triacetin, tributyrin, p-nitrophenylacetate, and lyso-phosphatidylcholine, as well as esters of cholesterol and of vitamins A, Dj, and E and glycerides solubilized by bile salts. Its molecular weight (approximately 100,000) is greater than that of the rat or pig enzyme, and it can hydrolyze... 

Retinol formed by retinyl ester hydrolysis (or originating as such in the diet) and dietary -carotene are solubilized in mixed micelles as discussed above, thus enabling these molecules to reach the microvillus membrane. In studies with everted rat gut sacs in vitro, El-Gorab et al. (1975) reported that micellar solutions significantly enhance uptake of both retinol and p-carotene over emulsions. Maximal uptake occurred at the critical micellar concentration of the bile salt mixture. At higher detergent concentrations, 3-carotene uptake declined whereas retinol absorption remained high. 

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. 

Retinyl ester stored in the liver must be hydrolyzed before the retinol can be mobilized from the liver as the retinol-RBP complex. Information is needed as to whether or not the processes of retinyl ester hydrolysis and of RBP production and secretion might, under some circumstances, be coordinated in some way. The question to be asked is whether or not the hydrolysis of retinyl esters might at times serve as one of the regulatory steps in the overall process of retinol mobilization from the liver. Information available about the enzymatic hydrolysis of retinyl esters in liver is reviewed in Chapter 7. 

Other factors that may affect the availability of retinol for complex formation with apo-RBP are (1) the manner in which retinol is transported within the cell from the site(s) of retinyl ester hydrolysis to a molecule of apo-RBP and (2) the manner in which the retinol molecule is presented to the membrane-bound molecule of apo-RBP. In this regard, the possible roles of cellular retinol-binding protein (CRBP) and of the so-called cytosol retinyl ester lipoprotein complex in delivering retinol to apo-RBP need exploration (Chen et al., 1981 Sklan et al., 1982). More information is also needed about the movement of retinol between hepatocytes and fat-storing cells (lipocytes) under normal and abnormal conditions. These various topics are also reviewed in Chapter 7. 

Boerman MHEM, Napoli JL (1991) Cholate-independent retinyl ester hydrolysis stimulation by apo-cellular retinol binding protein. J Biol Chem 266 22 273-22 278... 

Rgure 5 The effect of apo-CRBP(l) on the rates of retinol esterification (lecithin retinol acyltransferase (LRAT)) and retinyl ester hydrolysis (REH). 

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... 

E. H. Harrison, Enzymes Catalysing the Hydrolysis of Retinyl Esters , Biochim. Biophys. Acta 1993, 1170, 99-108. 

Hydrolysis of retinyl ester to retinol occurs in the lumen of the small intestine from where it is absorbed with the aid of bile salts, esterified to form retinyl ester and then released into lymph where it is incorporated into chylomicrons. The action of lipoprotein lipase converts chylomicrons to remnants and the retinyl ester remains in the remnants to be taken up by the Uver, where it is stored as the ester until required. On release from the liver, it is transported in blood bound to retinal binding-protein. 

Apo-CRBP(I) stimulates the hydrolysis of retinyl esters, thus releasing retinol from stores for transfer to RBP. This means that the esterification and... 

Blaner WS, Obunike JC, Kurlandsky SB, al-Haideri M, Piantedosi R, Deckelbaum RJ, and Goldberg IJ (1994) Lipoprotein lipase hydrolysis of retinyl ester. Possible implications for retinoid uptake by cells. Journal of Biological Chemistry 269,16559-65. 

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