Endoplasmic reticulum 3-glucuronidase

Three isoenzymes of carboxylesterase were purified from rat liver micro-somes and were named RL1, RL2, and RH1. These differ from each other in their response to hormone treatment, inducibility, substrate specificity, and immunological properties [75], It was shown that RL1, RL2, and RH1 resemble hydrolases p/ 6.2/6.4, pI 6.0, and pI 5.6, respectively. Enzyme RL2 was found to be identical to egasyn, a protein with esterase activity found in the endoplasmic reticulum [76], The role of egasyn is to stabilize glucuronidase (EC 3.2.1.31) by noncovalent binding to the microsomal membrane. 

FIG. 2. Schematic representation of the release of P-glucuronidase (pG) from hepaiocyie.s lo blood by OP administration in animals. EG, egasyn OP. organophosphate ER. endoplasmic reticulum. 

It is perhaps significant that microsomal vesicles derived from the endoplasmic reticulum exhibit conjugases and hydrolases in an analogous fashion. For example, glucuronyltransferase and /3-glucuronidase are pairs which have been found in association wiffi endoplasmic reticulum (Pogell and Leloir, 1961). 

Dual localization of 3-glucuronidase in endoplasmic reticulum and lysosomes was demonstrated by Fishman et al. (1967b) by using two methods of cytobiochemistry. From these findings it has been suggested that S-glueuronidase may serve as a structural protein of the endoplasmic reticulum. 

The discussion will lirst consider the chemical reaction catalyzed by y3-glucuronidase and will also deal with the function of /J-glucuronidase located either in the endoplasmic reticulum or in the lysosome of the cell. Tlie role of -glucuronidase in body fluid, especially intestinal contents and urine, will then be discussed. An interpretation follows of some of the phenomena discussed earlier in the chapter based on the concepts relating to the function of /3-gIucuronidase. 

In summary, therefore, the rise of /3-glucuronidase activity (per se) measured in homogenate may reflect an increa.se in either endoplasmic reticulum enzyme, an increase in lysosomal enzyme, or in both. Before the interpretation of such an increase can be made exact, it is necessary to establish how much of the enzyme is coming from each subecllular location. 

There is a recent, detailed account of methods for preparing and characterizing the components of the endoplasmic reticulum (DePierre and Dallner, 1976). Table 2 lists a number of enzymes associated with the endoplasmic reticulum. Several of these enzymes have been localized to the cytoplasmic surface of the reticular membranes, including cytochrome NADH-cytochrome bs-reductase, Mg " -ATPase, 5 -nucleotidase, nucleoside pyrophosphorylase, and GDP-mannosyl transferase. A number of others, including nucleoside diphosphatase, glucose-6-phosphatase, acetanilide-hydrolyzing esterase, and -glucuronidase have been localized to the luminal surface (DePierre and Ems-ter, 1977). Cytochrome P-450 appears to be present at both the cytoplasmic and luminal surfaces. 

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