Gamma-glutamyl transferase ectoactivity in the intact rat liver: effect of chronic alcohol consumption

The localization of gamma-glutamyl transferase (GGT) in the intact rat liver was studied by a new approach in which the chromogenic gamma-glutamyl donor substrate of GGT gamma-glutamyl-p-nitroanilide is perfused through the portal vein to yield p-nitroaniline, which is monitored spectrophotometrically. GGT activity was markedly increased by the gamma-glutamyl acceptors glycyl-glycine, cystine and methionine, following Michaelis-Menten kinetics. Infusion of glutathione (GSH), the natural substrate of GGT, was shown to markedly reduce or to abolish the formation of p-nitroaniline without entering the liver cells, indicating the existence of a GGT ectoactivity accessible to the sinusoidal circulation. This ectoenzyme was shown to remove significant amounts of GSH from the circulation, amounting, in the naive rat, to 20-25% of the net rate at which GSH is contributed by the liver into the circulation. Chronic alcohol consumption is known to increase hepatic GGT activity, although the biological significance of such an effect remains unknown. Present studies show that chronic administration of alcohol to rats leads to a significant (40-75%) increase in hepatic GGT ectoactivity. GGT ectoactivity significantly correlates with total liver GGT, both in control and alcohol-treated animals (r = .76 and r = .90, respectively). Livers of alcohol-fed rats showed an increased (80-110%) capacity to remove circulating GSH which strongly correlated with total liver GGT (r = .96; p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)