Mechanism of biosynthesis of thio-β-d-glucuronides and thio-β-d-glucosides

Abstract

1. The thio-β-d-glucosiduronic acids (thio-β-glucuronides) of o-aminothiophenol, diethyldithiocarbamic acid, p-nitrothiophenol and thiophenol are formed biosynthetically in broken- and intact-cell preparations of mouse liver. 2. For this biosynthesis to occur in homogenates or microsomal fractions, UDP-glucuronic acid was required during incubation; glucose, glucuronic acid or UDP could not replace it. UDP was a product of the reaction. 3. The biosynthetic mechanism linking glucuronic acid to thiol and carbodithioic groups therefore requires UDP-glucuronyltransferase activity and resembles that forming the various types of O-glucuronides. 4. An analogous enzymic mechanism employing UDP-glucose synthesizes the thio-β-d-glucosides of diethyldithiocarbamic acid and thiophenol in gut preparations of the mollusc Arion ater; this mechanism resembles that forming the O-glucosides. The thio-β-d-glucosides are formed also in intact cells. 5. As expected from the distribution of O-glycosides, S-glucuronides of these aglycones were not detectable with the invertebrate, nor were the S-glucosides with the vertebrate. 6. Despite their similar biosyntheses, S- and O-β-glycosides differ in susceptibility to hydrolysis by β-glycosidases. Rat preputial-gland β-glucuronidase hydrolysed thioglucuronides of o-aminothiophenol, diethyldithiocarbamic acid and p-nitrothiophenol, hydrolysis being inhibited by glucarolactone; the thioglucuronide of thiophenol was not hydrolysed by preputial-gland or liver β-glucuronidase. The two S-glucosides resisted hydrolysis by β-glucosidase from almond emulsin.