3hydroxykynurenine

3-Hydroxykynurenine (3-HK) is a metabolite of tryptophan in the kynurenine pathway of its catabolism. It is formed from kynurenine by the enzyme kynurenine 3-monooxygenase (KMO) and represents an intermediate toward downstream metabolites such as 3-hydroxyanthranilic acid and quinolinic acid, which feed into nicotinamide adenine dinucleotide (NAD+) biosynthesis.

Biosynthesis and metabolism: After its formation, 3-HK is commonly converted by kynureninase to 3-hydroxyanthranilic acid, which is subsequently converted to quinolinic acid and then to NAD+. The pathway also branches toward kynurenic acid via other enzymes. 3-HK is produced in both brain and peripheral tissues, and its production is often enhanced under inflammatory conditions that activate KMO.

Biological significance: 3-HK can act as a pro-oxidant. Through redox cycling, it can generate reactive oxygen species and contribute to oxidative stress, particularly in the central nervous system. Elevated 3-HK levels have been observed in several neurological and psychiatric conditions associated with inflammation and kynurenine pathway activation, though its precise role is context-dependent.

Clinical and research relevance: 3-HK is commonly measured in plasma, CSF, or tissue as a biomarker of kynurenine pathway activity. It is studied to understand links between tryptophan metabolism, neuroinflammation, and disorders such as neurodegeneration and mood disturbances.