Disease relevance of Kynu

• KYNU seems to be one of the genes that contributes to hypertension in SHR [1].
• The cosegregation analysis indicated that only the kynureninase gene (KYNU) polymorphism influenced systolic blood pressure (SBP) and residuals of systolic blood pressure after adjusting for heart rate and body weight (RSBP) [1].
• Cloning, sequence, and expression of kynureninase from Pseudomonas fluorescens [2].
• The resultant plasmid was used to transform E. coli DH5alpha F', and these cells overexpressed kynureninase to about 37% of total soluble protein [2].
• During this phase of the skin disease tryptophan pyrrolase activity is significantly increased and kynureninase activity significantly decreased in liver in respect to the control animals [3].

Psychiatry related information on Kynu

• This makes kynureninase a possible therapeutic target for diseases such as Huntington's, Alzheimer's and AIDS related dementia, and the development of potent inhibitors an important research aim [4].

High impact information on Kynu

• Inactivation of the enzyme by substrates which undergo beta-elimination results in loss of kynureninase activity, but kynurenine does not inactivate the enzyme [5].
• This investigation demonstrates that rat hepatic cysteine conjugate beta-lyase is the same enzyme as kynureninase [5].
• Kynureninase is an enzyme which plays a key role in the biosynthesis of nicotinamide ribonucleotides [5].
• Kynurenine 3-hydroxylase and quinolinic acid phosphoribosyltransferase were unchanged, but the activities of kynureninase, 3-hydroxyanthranilate dioxygenase, and aminocarboxymuconate-semialdehyde decarboxylase (ACMSDase) were significantly decreased [6].
• Lesion-induced increases of the activities of kynurenine-3-hydroxylase (3.6-fold), kynureninase (7.6-fold), kynurenine aminotransferase (1.8-fold), and 3-hydroxyanthranilic acid oxygenase (4.2-fold) likely contributed to the enhanced flux through the pathway in the lesioned striatum [7].

Chemical compound and disease context of Kynu

• Vitamin B-6 status was evaluated according to several biological criteria (weight gain, urinary excretion of xanthurenic acid after tryptophan loading, plasma pyridoxal 5'-phosphate, apparent pyridoxal 5'-phosphate-saturation of liver kynureninase, urinary excretion of 4-pyridoxic acid and fecal output of vitamin B-6) [8].
• RESULTS: Two new kynurenine analogues, 3-hydroxydesaminokynurenine and 3-methoxydesaminokynurenine, were synthesised as inhibitors of kynureninase and tested on the tryptophan-induced bacterial enzyme from Pseudomonas fluorescens, the recombinant human enzyme and the rat hepatic enzyme [4].

Biological context of Kynu

• By tryptic and CNBr digestion of purified rat liver kynureninase, we obtained about 28% of the amino acid sequence of the enzyme [9].
• Profile analysis of kynureninase primary structure indicated the presence of a pyridoxal-P-binding site consensus sequence assigned to class-V aminotransferases, with Lys276 being the residue binding the cofactor [10].
• Degenerate oligonucleotides designed from the amino acid sequences of peptides from rat liver kynureninase, were used as primers for reverse-transcription PCR of rat kidney RNA [10].
• After transfection of HEK-293 cells with the cDNA coding for kynureninase, the K(m) values of L-kynurenine and DL-3-hydroxykynurenine for the recombinant enzyme were 671 +/- 37 microM and 13.2 +/- 2.0 microM, respectively [10].
• This association with blood pressure decreased in proportion to the distance from KYNU [1].

Anatomical context of Kynu

• Interestingly, COS-1 cells transfected with the cDNA coding for rat kynureninase also display cysteine-conjugate beta-lyase activity [9].
• Amino-acid sequence of kynureninase purified from rat liver cytosol was determined by an amino-acid sequencer [11].
• Kynureninase activity of hepatocytes from starved rats was 50% greater than that of cells from fed rats [12].
• The remainder of the control for tryptophan degradation was associated with the transport of the amino acid across the plasma membrane, with only very small contributions from kynureninase and kynurenine hydroxylase [13].
• The co-administration of m-nitrobenzoylalanine (20 nmols into the hippocampus), an inhibitor of kynurenine hydroxylase and kynureninase, together with a systemic injection of the compound (100 mg kg(-1), i.p.), afforded some protection against kainate, reducing cell loss from 91 to 48% [14].

Associations of Kynu with chemical compounds

• Kynureninase [E.C.3.7.1.3.] is one of the enzymes involved in the biosynthesis of NAD cofactors from tryptophan through the kynurenine pathway [9].
• Kynureninase (L-kynurenine hydrolase), a pyridoxal-5'-phosphate-(pyridoxal-P)-dependent enzyme, catalyses the cleavage of L-kynurenine and L-3-hydroxykynurenine into anthranilic and 3-hydroxyanthranilic acids, respectively [10].
• The homology search between this enzyme and the other pyridoxal phosphate-dependent enzymes showed that kynureninase was similar to mitochondrial aspartate aminotransferase, and also to cystathionine gamma-synthase and gamma-lyase to a lesser extent [11].
• Product inhibitors of kynureninase, anthranilate, and 3-hydroxyanthranilate are also inhibitors of cysteine conjugate beta-lyase [5].
• Several kynurenine analogues were synthesized and tested as inhibitors of the enzymes kynurenine hydroxylase and/or kynureninase with the aim of identifying new compounds able to inhibit the synthesis of quinolinic acid (an endogenous excitotoxin) and to increase that of kynurenic acid, an endogenous antagonist of ionotropic glutamate receptors [15].

Other interactions of Kynu

• KYNU was found to be located on rat chromosome 3, and quantitative trait loci analysis at this locus indicated that the logarithms of the odds scores for KYNU in terms of SBP and RSBP were 2.0 and 3.3, respectively [1].
• Increases in flux through kynureninase (EC 3.7.1.3) and to acetyl-CoA can be explained in terms of increased substrate supply from tryptophan 2,3-dioxygenase [16].
• The sensitivity of the three pathways to pyridoxine deprivation is interpreted and discussed in terms of the different affinities for pyridoxal phosphate and the control strengths of the pyridoxal phosphate-dependent enzymes, tyrosine aminotransferase and kynureninase [17].
• Kynurenine aminotransferase, kynureninase and 3-hydroxyanthranilate-3,4-dioxygenase activity was diminished or unchanged, while the activity of kynurenine 3-hydroxylase was significantly increased [18].

Analytical, diagnostic and therapeutic context of Kynu

• Northern blot analysis revealed the synthesis of a 2.0 kb rat kynureninase mRNA [9].
• Kynureninase activity was measured in various organs of the rat by a sensitive assay method based on the use of an HPLC system [19].

References