Quinolinic acid

A neurotoxic breakdown product of the kynurenine pathway – an NMDA agonist. Raised with inflammation; in studies, raised values have been observed in inflammatory diseases of the nervous system, in depression and in neurodegenerative diseases.

What quinolinic acid does in the body

Quinolinic acid is formed at the end of the KMO branch: from 3-hydroxyanthranilic acid an iron-dependent enzyme forms an unstable intermediate, which closes spontaneously into quinolinic acid. Quinolinate phosphoribosyltransferase (QPRT) converts it into the precursor of NAD⁺ – quinolinic acid is thus the building block through which the body makes NAD⁺ from tryptophan. In the brain it is formed mainly by microglia and macrophages that have migrated there. At the same time quinolinic acid stimulates NMDA receptors, especially those with the NR2A and NR2B subunits. It also increases the release of glutamate, inhibits its reuptake into astrocytes and forms complexes with iron that oxidise fats in cell membranes.

Low quinolinic acid – what happens in the body?

Little quinolinic acid is formed when the kynurenine pathway runs at a calm pace without an inflammatory stimulus, or when a larger share of the intermediate is diverted via the enzyme ACMSD to picolinic acid. NMDA receptors are then hardly stimulated additionally from this side. Less starting material from tryptophan is available for NAD⁺ production; the body then uses more niacin and nicotinamide from food.

High quinolinic acid – what happens in the body?

When macrophages and microglia are activated by interferon-γ and other inflammatory messengers, they form considerably more quinolinic acid via IDO and KMO. QPRT can only process limited amounts further, so quinolinic acid accumulates. It then stimulates NMDA receptors persistently: calcium flows into nerve cells, mitochondria are put under strain and reactive oxygen species are formed. With ongoing overstimulation, nerve cells can be damaged – this process is called excitotoxicity. Raised values have been observed in studies in infections of the nervous system, in depression with raised inflammatory markers and in neurodegenerative diseases.

The interpretation is given in your report.