Tryptophan Metabolism in Rat Liver After Administration of Tryptophan, Kynurenine Metabolites, and Kynureninase Inhibitors
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 kynureninase 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.
International journal of tryptophan research IJTR