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.