Diazobenzenesulphonate selectively abolishes stimulation of glucuronidation by UDP-N-acetylglucosamine.
1. Basal rates of glucuronidation of oestrone (guinea pig) or of 4-nitrophenol (rat or guinea pig) were not significantly altered in sealed liver microsomal vesicles, treated with the membrane-impermeant protein-modifying agent diazobenzenesulphonate at 0.5-1.0 mM. 2. Contrarily, diazobenzenesulphonate abolished the normal stimulation of glucuronidation by UDP-N-acetylglucosamine. 3. Ultrasonication to increase microsomal permeability activated glucuronidation by 680-750% and permitted significant inhibition by diazobenzenesulphonate. 4. These findings are consistent with a model wherein glucuronyltransferases are embedded in the luminal leaflet of the endoplasmic reticulum and access of UDP-glucuronic acid to the transferases is facilitated by transmembrane carriers, which are stimulated by UDP-N-acetylglucosamine and are available to diazobenzenesulphonate; ultrasonication serves to permit access of diazobenzenesulphonate to glucuronyltransferases themselves, resulting in inhibition of their activity.
D000818:Animals; D001557:Benzenesulfonates / Q000494:pharmacology*; D003979:Diazonium Compounds / Q000494:pharmacology*; D004970:Estrone / Q000378:metabolism; D005965:Glucuronates / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009596:Nitrophenols / Q000378:metabolism; D051381:Rats; D013268:Stimulation, Chemical; D013425:Sulfanilic Acids / Q000031:analogs & derivatives / Q000494:pharmacology*; D014465:Ultrasonics; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000494:pharmacology*; D014539:Uridine Diphosphate Sugars / Q000494:pharmacology*
D001557:Benzenesulfonates; D003979:Diazonium Compounds; D005965:Glucuronates; D009596:Nitrophenols; D013425:Sulfanilic Acids; D014539:Uridine Diphosphate Sugars; D004970:Estrone; D014537:Uridine Diphosphate N-Acetylglucosamine; C000469:diazobenzenesulfonic acid