3-Hydroxykynurenine

Intermediate of the kynurenine pathway between kynurenine and quinolinic acid. Raised when KMO works harder – for example with inflammation – or when vitamin B6 is scarce; it forms reactive oxygen species itself, and its oxidation products are linked with changes in nerve cells and lens proteins.

What 3-hydroxykynurenine does in the body

3-hydroxykynurenine is formed when the enzyme kynurenine 3-monooxygenase (KMO) on the outer mitochondrial membrane converts kynurenine using oxygen and NADPH; KMO needs FAD, the active form of vitamin B2, for this. It is formed mainly in the liver and kidneys, and in the brain in microglial cells and in macrophages that have migrated there. Kynureninase then uses vitamin B6 to split it into 3-hydroxyanthranilic acid, which becomes quinolinic acid and finally NAD⁺ over further steps. A smaller part is converted – also with vitamin B6 – into xanthurenic acid. 3-hydroxykynurenine oxidises easily and in doing so releases hydrogen peroxide and other reactive oxygen species; in the lens of the eye, derivatives of it serve as filters against UV light.

Low 3-hydroxykynurenine – what happens in the body?

Little 3-hydroxykynurenine is formed when KMO converts little kynurenine – for example in the absence of an inflammatory stimulus, or when vitamin B2 is scarce and KMO lacks FAD. Kynurenine then flows more into the other branches: towards kynurenic acid, which tends to dampen nerve cells, and towards anthranilic acid. Less starting material for the body's own NAD⁺ production is then formed via 3-hydroxykynurenine; the body relies more on niacin from food. For the cells, a low value also means less oxidative burden from this metabolic step.

High 3-hydroxykynurenine – what happens in the body?

A lot of 3-hydroxykynurenine is formed when inflammatory messengers such as interferon-γ, TNF-α and IL-6 first upregulate tryptophan breakdown via IDO and then KMO in macrophages and microglia. It also builds up when vitamin B6 is scarce, because kynureninase and the conversion into xanthurenic acid then run more slowly. When it oxidises, 3-hydroxykynurenine forms reactive oxygen species that attack fats in cell membranes, proteins and genetic material; nerve cells are particularly sensitive to this, and lens proteins can be altered by its oxidation products. Raised values have been observed in studies in neurodegenerative diseases and in depression with raised inflammatory markers.

The interpretation is given in your report.