High impact information on Haao

• 3-Hydroxyanthranilic acid oxygenase (3HAO) is the biosynthetic enzyme for quinolinic acid, an endogenous agonist of the NMDA glutamate receptor subtype and a potent neurotoxin [1].
• The highest density of 3HAO-i cells was found in the molecular layer of Ammon's horn and in the hilus of area dentata, while the granular cell layer of area dentata and stratum pyramidale of Ammon's horn contained the lowest number of 3HAO-stained cells [2].
• The observation that 3HAO and QPRT only partially coexist in hippocampal glial cells suggests that while synthesis and catabolism of QUIN may occur in the same glial cells, catabolism of QUIN can also take place in cells lacking the synthetic enzyme.(ABSTRACT TRUNCATED AT 400 WORDS)[2]
• Cells containing 3HAO immunoreactivity (3HAO-i) were present in all subfields of the hippocampal region, including the area dentata, Ammon's horn, the subicular complex, and the entorhinal area [2].
• Kinetic analyses of both pure liver and partially purified brain 3HAO revealed an identical Km of 3 microM for the substrate 3-hydroxyanthranilic acid [3].

Biological context of Haao

• Specific, reversible, and tightly binding 3HAO inhibitors can be expected to become valuable tools for the study of quinolinate neurobiology [4].
• QSAR study on inhibition of brain 3-hydroxy-anthranilic acid dioxygenase (3-HAO): a molecular connectivity approach [5].

Anatomical context of Haao

• 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 [6].
• The two enzymes were differentially expressed by astrocytes in a complementary pattern: 3HAO staining was strongest at the glomerular-external plexiform layer junction; QPRT staining was strongest at the glomerular-olfactory nerve layer junction [7].
• The large increases in striatal enzyme activities after 7 days were accompanied by smaller increases in both 3-HAO and QPRT activities in the ipsilateral substantia nigra [8].
• No changes in the activity of hippocampal 3-HAO or QPRT were noted 7 or 60 days after cholinergic deafferentation by fornix-fimbria transection nor were any changes observed in the contralateral hippocampus at any time-point following the ibotenate lesion [9].

Associations of Haao with chemical compounds

• In order to explore the anatomical basis of possible functional interactions between glutamate and quinolinic acid in the rat striatum, pre- and postembedding immunocytochemical methods were used to localize 3HAO immunoreactivity (-i) and glutamate-i at the electron microscopic level [1].
• Effect of excess leucine on tryptophan oxygenase, 3-hydroxyanthranilate oxygenase and leucine aminotransferase in livers of young rats [10].
• The kynurenine pathway intermediate 3-hydroxyanthranilic acid (3-HANA) is converted by 3-HANA 3,4-dioxygenase (3-HAO) to the pro-convulsive excitotoxin quinolinic acid [11].
• In contrast to the high activity of 3-hydroxyanthranilate 3,4-dioxygenase, aminocarboxymuconate-semialdehyde decarboxylase is 30-35 times less active, showing the efficiency of conversion of tryptophan to NAD [12].
• Non-competitive inhibition of 3-hydroxyanthranilate-3,4-dioxygenase by 4-chloro-3-hydroxyanthranilic acid in whole brain of rat [13].

Other interactions of Haao

• Tryptophan oxygenase (EC 1.13.1.12), 3-hydroxyanthranilate oxygenase (EC 1.13.1.6) and leucine aminotransferase (EC 2.6.1.6) activities were determined in livers of rats subjected to different dietary restrictions, with and without excess leucine [14].
• Kynurenine aminotransferase, kynureninase and 3-hydroxyanthranilate-3,4-dioxygenase activity was diminished or unchanged, while the activity of kynurenine 3-hydroxylase was significantly increased [15].
• However, the more active enzymes appeared to be kynurenine 3-monooxygenase and 3-hydroxyanthranilate 3,4-dioxygenase [12].

References