Retinyl esters enzymatic hydrolysis

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... 

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. 

Studies from the authors laboratory have provided more detailed information about the enzymatic hydrolysis of retinyl esters in rat liver. In the initial work (Harrison et al., 1979), the hydrolysis of retinyl palmitate was explored with liver homogenate fractions from retinol-depleted, retinoic acid-fed rats. Retinol-depleted animals were used in order to avoid the problem posed by large and variable amounts of endogenous substrate (retinyl esters) present in the liver of normal animals. Retinyl palmitate hydrolase (RPH) activity was maximal near pH 8 and required a bile salt for stimulation. The enzymatic activity showed an unusual subcellular distribution, with about 40% of total RPH activity recovered... 

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. 

The enzymatic hydrolysis of retinyl esters in liver has been examined in retinol-depleted, retinoic acid-supplemented rats (Harrison et al., 1979) as well as in normal rats (Prystowsky et al., 1981). In both studies, the enzyme retinyl palmitate hydrolase showed an unusual subcellular distribution, being found in the nuclear, mitochondrial, and supernatant fractions and displayed a large variability in activity from rat to rat. For additional information regarding the esterification and hydrolysis of retinol the reader is again referred to Chapters 7 and 10. 

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