Medda_1987_Cell_50_301

Organophosphorous compounds, which are potent inhibitors of egasyn-esterase activity, caused a rapid dissociation of the high molecular weight egasyn-microsomal beta-glucuronidase complex when administered in vivo or when added in vitro to microsomal suspensions. The dissociation was relatively specific to phosphodiester inhibitors of the esterase active site. Also, the egasyn-esterase active site was inaccessible to substrates and to inhibitors when egasyn was complexed to beta-glucuronidase. Dissociation of the egasyn-microsomal beta-glucuronidase complex in vivo by organophosphorous compounds was followed by massive and rapid secretion of microsomal beta-glucuronidase, but not egasyn, into plasma. These experiments implicate the egasyn-esterase active site in attachment of microsomal beta-glucuronidase to egasyn by a novel mechanism that, in turn, compartmentalizes beta-glucuronidase within the endoplasmic reticulum.