Retinyl palmitate hydrolase

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... 

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. 

Blaner WS, Smith JE, Dell RB, Goodman DS (1985) Spatial distribution of retinol-binding protein and retinyl palmitate hydrolase activity in normal and vitamin A deficient rat livers. J Nutr 115 856-864... 

Tsin ATC, Chambers JP, Garcia MH, Flores JM (1986) Decreased hepatic retinyl palmitate hydrolase activity in protein-deficient rats. Biochim Biophys Acta 878 20-24... 

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... 

Fig. 1. The structures of key retinoids and their precursors. Fish convert retinyl esters (e.g. retinyl palmitate (RP)) and carotenoids (e.g. /3-carotene) to retinol in the gut lumen prior to intestinal absorption. Retinyl esters (e.g. RP) stored in the liver are synthesized from retinol by lecithin retinol acyltransferase (LRAT) and acyl CoAiretinol acyltransferase (ARAT). The retinyl esters are mobilized through their conversion to retinol by retinyl ester hydrolase (REH), which is then transported in the circulation to various sites in the body. Retinol is further metabolized within specific tissues to retinal by alcohol dehydrogenases (ADH) or short-chain dehydrogenase/reductase. Retinal is converted to the two major biologically active forms of retinoic acid (RA) (all-trans and 9-cis RA). Retinaldehyde dehydrogenase 2 (Raldh2) synthesizes all-trans RA from all-trans precursors and 9-cis RA form 9-cis precursors.

Napoli JL, Pacia EB, Salerno GJ (1989) Cholate-independent hydrolysis of all-fraw -retinyl palmitate by rat tissues solubilization of multiple kidney microsomal hydrolases. Arch Biochem Biophys 21 A 192-199... 

Harrison EH, Gad M (1989) Hydrolysis of retinyl palmitate by enzymes of rat pancreas and liver differentiation of bile salt-dependent and bile salt-independent, neutral retinyl ester hydrolases in rat i ct.J Biol Chem 264 17 142-17 147... 

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