KMO activity index

KMO channels kynurenine towards 3-OH-kynurenine → quinolinic acid (neurotoxic). A raised index shows that more kynurenine is flowing into the branch towards 3-OH-kynurenine and quinolinic acid, as occurs with inflammation.

What the KMO activity index shows

Kynurenine stands at a fork in the road. The kynurenine aminotransferases (KAT) use vitamin B6 to make kynurenic acid from it, kynureninase makes anthranilic acid, and kynurenine 3-monooxygenase (KMO) makes 3-hydroxykynurenine, the precursor of quinolinic acid and NAD⁺. The KMO activity index relates the product of KMO to its starting material, kynurenine. It is therefore not a measurement of the enzyme itself, but shows what share of kynurenine is currently flowing into the branch towards 3-hydroxykynurenine and quinolinic acid – and how much remains for the branch towards kynurenic acid.

Low KMO activity index – what happens in the body?

When the index is low, relatively little kynurenine is converted via KMO. More kynurenine is then available for kynurenic acid, which dampens the effect of glutamate at NMDA receptors and slows the release of glutamate and acetylcholine. A low index occurs when there is little inflammatory stimulus, or when vitamin B2 is scarce, because KMO needs FAD as a cofactor. In studies, a predominance of the kynurenic acid branch has been linked to changes in attention and memory.

High KMO activity index – what happens in the body?

When the index is high, a large share of kynurenine flows into the branch towards 3-hydroxykynurenine and quinolinic acid. This happens mainly when inflammatory messengers activate macrophages and microglia. 3-hydroxykynurenine forms reactive oxygen species when it oxidises, and quinolinic acid stimulates NMDA receptors; at the same time less kynurenine remains for the dampening kynurenic acid. The balance between dampening and stimulating metabolites thus shifts towards the stimulating side. In studies, a high share of this branch has been observed in depression with raised inflammatory markers and in neurodegenerative diseases.

The interpretation is given in your report.