AJP - Gastrointestinal and Liver Physiology, Vol 253, Issue 1 86-G92, Copyright © 1987 by American Physiological Society
Age-dependent biliary excretion of glutathione-related thiols in rats: role of gamma-glutamyltransferase
Z. Gregus, A. F. Stein and C. D. Klaassen
The role of gamma-glutamyltransferase (GGT) in the biliary excretion of
glutathione (GS) was studied in rats during postnatal development. Between
2 and 10 wk of age the biliary excretion of GS-related sulfur increased
ninefold. During this period, alterations were observed in both hepatic GGT
and the composition of GS-related thiols and disulfides in bile. For
instance, between 3 and 4 wk of age, GGT activity and the biliary excretion
of GS hydrolysis products (Cys-Gly and Cys) increased markedly, and the
latter became the predominant sulfhydryls in bile. However, by 10 wk of
age, the excretion rate of GS increased and exceeded the rate of excretion
of Cys-Gly and Cys. The parallelism between hepatic GGT activity and the
biliary excretion of GS-hydrolysis products during development suggests a
role for GGT in the formation of biliary Cys-Gly and Cys. Furthermore, in
4-wk-old rats, inhibition of hepatic GGT by acivicin markedly decreased the
biliary excretion of Cys-Gly and Cys and increased that of GS without
influencing the excretion of total GS-related sulfur in bile. The biliary
excretion of GS-related thiols was less responsive to acivicin in 2- and 7-
to 10-wk-old rats, suggesting that GGT plays a smaller role in influencing
biliary thiol composition at those ages. In summary, GS transported into
bile is hydrolyzed in an age-dependent manner, however, the GGT-initiated
hydrolysis of GS does not affect the biliary excretion of total thiols in
rats.
