title: Tryptophan Metabolism in Rat Liver After Administration of Tryptophan, Kynurenine Metabolites, and Kynureninase Inhibitors.
abstract: Rat liver tryptophan (Trp), kynurenine pathway metabolites, and enzymes deduced from product/substrate ratios were assessed following acute and/or chronic administration of kynurenic acid (KA), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid (3-HAA), Trp, and the kynureni-nase inhibitors benserazide (BSZ) and carbidopa (CBD). KA activated Trp 2,3-dioxygenase (TDO), possibly by increasing liver 3-HAA, but inhibited kynurenine aminotransferase (KAT) and kynureninase activities with 3-HK as substrate. 3-HK inhibited kynureninase activity from 3-HK. 3-HAA stimulated TDO, but inhibited kynureninase activity from K and 3-HK. Trp (50 mg/kg) increased kynurenine metabolite concentrations and KAT from K, and exerted a temporary stimulation of TDO. The kynureninase inhibitors BSZ and CBD also inhibited KAT, but stimulated TDO. BSZ abolished or strongly inhibited the Trp-induced increases in liver Trp and kynurenine metabolites. The potential effects of these changes in conditions of immune activation, schizophrenia, and other disease states are discussed.
authors.affiliation: School of Health Sciences, Cardiff Metropolitan University, Cardiff, Wales, UK.
authors.forename: Abdulla A-B
authors.initials: AA
authors.lastname: Badawy
authors.affiliation: School of Health Sciences, Cardiff Metropolitan University, Cardiff, Wales, UK.; Present address: Department of Biochemistry, University of Karachi, Karachi, Pakistan.
authors.forename: Samina
authors.initials: S
authors.lastname: Bano
keywords: 3-dioxygenase; kynureninase; kynurenine aminotransferase; kynurenine pathway; tryptophan 2