Tryptophan and glucose metabolism in rat liver cells. The effects of dl-6-chlorotryptophan, 4-chloro-3-hydroxyanthranilate and pyrazinamide

Abstract

Liver cells pre-incubated with 1 mM-DL-6-chlorotryptophan are less sensitive to tryptophan-mediated inhibition of gluconeogenesis; this effect is apparent both at physiological (0.1 mM) and higher (0.5 mM) concentrations of tryptophan. 4-Chloro-3-hydroxyanthranilate (1-100 microM) has effects similar to those of DL-6-chlorotryptophan. The effects of both compounds are consistent with a decrease in quinolinate formation, a consequence of inhibition of 3-hydroxyanthranilate oxidase. Pyrazinamide (0.25-5.0 mM) significantly decreased flux through the glutarate pathway and potentiated tryptophan-mediated inhibition of gluconeogenesis; these changes were apparent at physiological concentrations of tryptophan. The effects of pyrazinamide are consistent with an increase in quinolinate formation resulting from inhibition of picolinate carboxylase.