Quinolinic acid: an endogenous inhibitor specific for type B monoamine oxidase in human brain synaptosomes.
Quinolinic acid (QUIN), a well-known excitotoxin, was found to inhibit type B monoamine oxidase (MAO-B) in human brain synaptosomal mitochondria. By kinetic analysis, the inhibition of MAO-B activity by QUIN was competitive with the substrate, kynuramine. On the other hand, type A MAO (MAO-A) activity in human brain synaptosomal mitochondria and human placental mitochondria was not affected by QUIN. The selective inhibition of MAO-B by QUIN was confirmed using human liver mitochondria; only MAO-B was inhibited by QUIN and MAO-A was not inhibited. The inhibition was completely reversible. Among compounds structurally related to QUIN, 4-pyrimidine carboxaldehyde was the most potent substrate-competitive inhibitor of MAO-B, while 3-hydroxyanthranilic acid and xanthrenic acid, other metabolites of tryptophan, inhibited MAO non-competitively with the substrate. The inhibition of MAO-B by QUIN may be related to the causes of the neurotoxicity of QUIN.
D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008996:Monoamine Oxidase Inhibitors; D011725:Pyridines / Q000494:pharmacology*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000201:enzymology
D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D011725:Pyridines; D011805:Quinolinic Acids; D017378:Quinolinic Acid