Tryptophan and glucose metabolism in rat liver cells. The effects of DL-6-chlorotryptophan, 4-chloro-3-hydroxyanthranilate and pyrazinamide.
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.
D015095:3-Hydroxyanthranilic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D005943:Gluconeogenesis / Q000187:drug effects*; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011718:Pyrazinamide / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D062367:ortho-Aminobenzoates; C026380:6-chlorotryptophan; D015095:3-Hydroxyanthranilic Acid; C026381:4-chloro-3-hydroxyanthranilic acid; D011718:Pyrazinamide; D014364:Tryptophan