Disease relevance of KYNU

• These results suggest roles for increased activities of IDO, kynurenine-3-hydroxylase and kynureninase in accelerating the synthesis of QUIN, L-KYN and KYNA in conditions of brain inflammation [1].
• One day after 10 min of cerebral ischemia, the activities of kynureninase and 3-hydroxy-3,4-dioxygenase were increased in the hippocampus, but local QUIN levels and the activities of the indoleamine-2,3-dioxygenase and kynurenine-3-hydroxylase were unchanged [2].
• Cloning, sequence, and expression of kynureninase from Pseudomonas fluorescens [3].
• The resultant plasmid was used to transform E. coli DH5alpha F', and these cells overexpressed kynureninase to about 37% of total soluble protein [3].
• Recombinant human kynureninase (L-kynurenine hydrolase, EC 3.7.1.3) was purified to homogeneity (60-fold) from Spodoptera frugiperda (Sf9) cells infected with baculovirus containing the kynureninase gene [4].

High impact information on KYNU

• Induction of spinal cord IDO (35.9-fold) accompanied smaller, but proportional increases in kynurenine-3-hydroxylase (2.4-fold) and kynureninase (2.3-fold) activities, which were correlated to CSF and tissue QUIN levels, as well as to measures of inflammatory lesions [1].
• Kynureninase activity was increased in the brain, lung, and duodenum, but not in the spleen, kidney, or liver [5].
• Kynurenine 3-hydroxylase and, in some cells, kynureninase and 3-hydroxyanthranilate 3,4-dioxygenase are important determinants of whether a cell can make quinolinate [6].
• Based on this alignment, we predict that Lys227 and Asp212 in P. fluorescens kynureninase are involved in pyridoxal-5'-phosphate binding [3].
• Alignment of the four sequences shows a highly conserved region which corresponds to the pyridoxal-5'-phosphate (PLP) binding site of rat kynureninase [3].

Chemical compound and disease context of KYNU

• Other chlamydiae (Chlamydia trachomatis, C. muridarum and Chlamydophila pneumoniae) lack genes encoding PRPP synthase, kynureninase, and either lack tryptophan-pathway genes altogether or exhibit various stages of reductive loss [7].

Biological context of KYNU

• We obtained the result that 3-hydroxyanthranilic acid content was significantly higher in the red phenotype than in the wild type, and kynureninase activity was also higher in the red phenotype [8].
• Chlamydophila psittaci was found to possess a compact operon containing PRPP synthase, kynureninase, and genes encoding all but the first step of tryptophan biosynthesis [7].

Anatomical context of KYNU

• Marked increases in the activity of kynureninase, kynurenine 3-hydroxylase, and 3-hydroxyanthranilate-3,4-dioxygenase were also detected in hippocampus but not in cerebellum on day 4 of recirculation [9].
• High activities of kynurenine 3-hydroxylase, kynureninase or 3-hydroxyanthranilate 3,4-dioxygenase were found in interferon-gamma-stimulated macrophages, THP-1 cells and SKHEP1 cells, and these cells made large amounts of quinolinate when supplied with L-tryptophan, L-kynurenine, 3-hydroxykynurenine or 3-hydroxyanthranilate [6].
• This indicates that lymphocyte kynureninase activity is depressed during a vitamin B6 deficiency [10].
• Kynurenine hydroxylase and kynureninase inhibitors as tools to study the role of kynurenine metabolites in the central nervous system [11].
• This quantitative difference in the ability to produce QUIN appears to be associated with a lower expression of 3 important enzymes of the KP in microglia: indoleamine 2,3-dioxygenase (IDO), kynureninase (KYNase) and kynurenine hydroxylase (KYN(OH)ase) [12].

Associations of KYNU with chemical compounds

• Mutation analysis of KYNU encoding kynureninase of the index case revealed homozygosity for a c.593 A > G substitution leading to a threonine-to-alanine (T198A) shift [13].
• Quinolinate production by human fetal brain cultures and U373MG cells was restricted by the low activities of kynurenine 3-hydroxylase, kynureninase and 3-hydroxyanthranilate 3,4-dioxygenase, and only small amounts of quinolinate were synthesized when cultures were supplied with L-tryptophan or 3-hydroxyanthranilate [6].
• P. fluorescens kynureninase also exhibits significant homology to the nifS gene product, cysteine desulfurase, and to eucaryotic serine/pyruvate aminotransferases, suggesting that it is a member of subgroup IV of the aminotransferase family of PLP-dependent enzymes [3].
• A series of novel bicyclic analogues of kynurenine were synthesised as inhibitors of kynureninase [14].
• S-aryl cysteine S,S-dioxides as inhibitors of mammalian kynureninase [15].

Other interactions of KYNU

• The kynurenine load test was introduced to distinguish, in vivo, between abnormal tryptophan metabolism caused by induction of tryptophan oxygenase or by impaired kynureninase function [16].

References