Disease relevance of 3-Hydroxyanthranilic acid

• Combined purification of actinomycin synthetase I and 3-hydroxyanthranilic acid 4-methyltransferase from Streptomyces antibioticus [1].
• In E. coli, this enzyme oxidizes 3-hydroxyanthranilate with a specific activity of 8 U/mg of protein [2].
• A novel degradative pathway of 2-nitrobenzoate via 3-hydroxyanthranilate in Pseudomonas fluorescens strain KU-7 [3].
• Cu,Zn.superoxide dismutase (SOD) enhanced the toxicity of 3-hydroxyanthranilic acid (3-HAT) to Salmonella typhimurium strain TA 102, evaluated as ability to form colonies [4].
• Increased levels of serum lipofuscin derived from 3-hydroxyanthranilic acid in patients with chronic renal failure [5].

High impact information on 3-Hydroxyanthranilic acid

• Selective inhibition of IFN gamma-induced formation of 3HAA by DPI caused reversion of the inhibitory action of this cytokine on both PBMC- and MDM-mediated LDL oxidation [6].
• Exogenous 3HAA added to PBMC or purified monocytes in the absence of IFN gamma also strongly and in a concentration-dependent manner inhibited LDL oxidation [6].
• 3-Hydroxyanthranilic-acid dioxygenase (3-HAO; 3-hydroxyanthranilate 3,4-dioxygenase, EC 1.13.11.6) is the enzyme that catalyzes the synthesis of QUIN from 3-hydroxyanthranilic acid, and evidence suggests that it could play a role in disorders associated with altered tissue levels of QUIN [7].
• In the late phase of acute PM, we found a significant transcriptional upregulation of kynurenine-3-hydroxylase and an accumulation of the neurotoxic metabolites 3-hydroxykynurenine (3-HKYN) and 3-hydroxyanthranilic acid in cortex and hippocampus [8].
• Levels of the free radical generators 3-hydroxykynurenine and 3-hydroxyanthranilic acid were decreased in HD patients, and hence did not appear to contribute to the oxidative stress [9].

Chemical compound and disease context of 3-Hydroxyanthranilic acid

• Metabolism of 14C-labeled tryptophan and 3-hydroxyanthranilic acid were administered to early hepatoma patients to evaluate the conversion of these precursors to niacin metabolites and to assess the effect of dietary supplementation with vitamin B-6, riboflavin, thiamin and vitamin C on the extent of conversion [10].
• Excretory abnormalities of either indican, kynurenine, 3-hydroxyanthranilic acid or indolylacryloylglycine have been occasionally combined with myopathy, seizures, liver and intestinal symptoms [11].

Biological context of 3-Hydroxyanthranilic acid

• Interferon-gamma inhibits human monocyte/macrophage-facilitated LDL lipid peroxidation via induction of cellular tryptophan degradation and production and release of 3-hydroxyanthranilic acid (3HAA) (Christen, S., Thomas, S. R., Garner, B., and Stocker, R. (1994) J. Clin. Invest. 93, 2149-2158) [12].
• The substrate specificity of the 23.8-kDa NbaC protein was found to be restricted to 3-hydroxyanthranilate [2].
• The NbaC enzyme carries out the oxidation of 3-hydroxyanthranilate to 2-amino-3-carboxymuconate-6-semialdehyde, while the NbaD enzyme catalyzes the decarboxylation of the latter compound to 2-aminomuconate-6-semialdehyde [2].
• In addition, the activities of complexes I, II and IV of the respiratory chain were significantly inhibited by 3HK, while 3HA inhibited complexes I and II activities and AA inhibited complexes I-III activities [13].
• Intermediate metabolites of tryptophan, 3-hydroxy-L-kynurenine (3-OHKY), 3-hydroxyanthranilic acid (3-OHAA) and anthranilic acid (AA), and an enzyme inhibitor from 3-OHKY to 3-OHAA, isonicotinic acid hydrazide (INH) with or without 3-OHKY at the maximum tolerated dose were injected s.c. to infant CDF1 mice [14].

Anatomical context of 3-Hydroxyanthranilic acid

• However, accumulation of QUIN was demonstrated in both cerebellum and hippocampus of control gerbils following an intracisternal injection of 3-hydroxyanthranilic acid, which verifies the availability of precursor to both regions when administered intracisternally [15].
• Involvement of oxidoreductive reactions of intracellular haemoglobin in the metabolism of 3-hydroxyanthranilic acid in human erythrocytes [16].
• Promotional effect of lithocholic acid and 3-hydroxyanthranilic acid on transformation of X-ray-initiated BALB/3T3 cells [17].
• However, inhibition of 3-HANA degradation by the specific 3-hydroxyanthranilic acid oxygenase blocker 4-chloro-3-hydroxyanthranilic acid (4-Cl-3-HANA; 10 microM) resulted in a rapid (within 2.5 min) doubling of 3-HANA levels in slices from cerebral cortex [18].
• Kinetic analysis of rat forebrain 3HAO revealed a Km of 3.6 +/- 0.5 microM for 3-hydroxyanthranilic acid and a Vmax of 73.7 +/- 9.5 pmol quinolinic acid/h/mg tissue [19].

Associations of 3-Hydroxyanthranilic acid with other chemical compounds

• Exposure of PBMC or MDM to IFN gamma induced the degradation of extracellular Trp with concomitant accumulation of kynurenine, anthranilic and 3-hydroxyanthranilic acid (3HAA) in the culture medium [6].
• Iron containing 3-Hydroxyanthranilate oxidase (3HAO) converts 3-hydroxyanthranilate (3HAA) and dioxygen into a precursor which spontaneously converts to quinolinic acid (QA) [20].
• Synthesis of quinolinic acid by 3-hydroxyanthranilic acid oxygenase in rat brain tissue in vitro [19].
• The final product was determined to be cinnabarinic acid as detected by spectrophotometry, paper chromatography and t.l.c. The formation of cinnabarinic acid from 3-hydroxyanthranilic acid in the cells was markedly inhibited by CO when intracellular haemoglobin was in a ferrous state, and by cyanide when it was in a ferric state [16].
• 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 [21].

Gene context of 3-Hydroxyanthranilic acid

• 3-Hydroxyanthranilic acid, one of l-tryptophan metabolites, inhibits monocyte chemoattractant protein-1 secretion and vascular cell adhesion molecule-1 expression via heme oxygenase-1 induction in human umbilical vein endothelial cells [22].
• In RAW 264.7 cells, the phenolic antioxidant 3-hydroxyanthranilic acid (OH-AA), but not anthranilic acid, inhibited citrulline synthesis by NOS II at sub-millimolar concentrations, when added 1 h before IFN-gamma and LPS [23].
• When monocytes were differentiated to immature DC in presence of either Trp or its metabolites kynurenine or 3-hydroxyanthranilic acid they expressed cell surface HLA-G, and Trp also increased shedding of HLA-G1 [24].
• RESULTS: Reduced levels of 5-HT and KYN intermediate metabolite 3-hydroxyanthranilic acid were found in serum of CSTB-deficient mice [25].
• Kinetic analyses of both pure liver and partially purified brain 3HAO revealed an identical Km of 3 microM for the substrate 3-hydroxyanthranilic acid [26].

Analytical, diagnostic and therapeutic context of 3-Hydroxyanthranilic acid

• As assessed by HPLC with electrochemical detection, 3-hydroxyanthranilic acid (3-HANA) was found to be present in the rat brain and peripheral organs [18].
• The product, 3-hydroxyanthranilic acid, was determined by isocratic high-performance liquid chromatography and fluorescence detection [27].
• A gas chromatographic method with alkali flame ionization detection is described for the determination of urinary total (free and conjugated) anthranilic acid (AA) and 3-hydroxyanthranilic acid (HAA) as their pentafluorobenzyl esters [28].
• Discontinuation of drug administration, with continued perfusion of 3-hydroxyanthranilic acid, revealed that the drug effect was reversible [29].
• To this end, QUIN's immediate bioprecursor 3-hydroxyanthranilic acid (30 microM) was applied through a microdialysis probe, and QUIN production was monitored hourly in the perfusate [29].

References