Drug conjugation in Gunn rats: reduced UDP-glucuronosyl transferase and UDP-glucosyl transferase activities with increased glycine-N-acyltransferase activity.

Abstract

Glucuronyl, glucosyl, glutathione, glycine conjugations and epoxide hydration were studied in livers of Wistar and Gunn rats. The activities of bilirubin UDP-glucuronosyl transferase and UDP-glucosyl transferase were reduced in microsomes of homozygous and heterozygous Gunn rats compared to Wistar rats (over 90 and 55-65%, respectively). Conjugation of 4-methylumbelliferone by UDP-glucuronosyl transferase was also reduced (30-35%) in Gunn rats. Treatment of microsomes in vitro with membrane perturbating agents increased the measurable activities but did not change the activity relationships between Wistar and Gunn rats. Microsomal epoxide hydrase and soluble glutathione-S-epoxide transferase activities occurred in Gunn rats at the Wistar level, but mitochondrial glycine-N-acyltransferase activity was elevated in homozygous and heterozygous Gunn rats (66 and 47%, respectively). The reciprocal velocity plots of UDP-glucuronosyl transferase activity were similarly concave in Gunn and Wistar rats.