3HAA

3-Hydroxyanthranilic acid (3HAA) is an aromatic amino acid–derived metabolite formed in the kynurenine pathway of tryptophan catabolism. It is commonly referred to as 3HAA and has the chemical formula C7H7NO3. It is also known as 2-amino-3-hydroxybenzoic acid.

Biosynthesis: In mammals, tryptophan is converted to N-formylkynurenine and then to kynurenine. Kynurenine is hydroxylated by kynurenine 3-monooxygenase to form 3-hydroxykynurenine, which is cleaved by kynureninase to yield 3-hydroxyanthranilic acid and alanine. 3-HAA is then oxidized by 3-hydroxyanthranilate 3,4-dioxygenase to 2-amino-3-carboxymuconate semialdehyde, which cyclizes to quinolinic acid, a precursor in de novo NAD+ biosynthesis.

Biological roles: 3HAA is an intermediate in tryptophan degradation and participates in redox chemistry, potentially influencing cellular oxidative stress. It serves as a substrate toward quinolinic acid, linking it to the NAD+ biosynthesis pathway. Levels of 3HAA can reflect activation of the kynurenine pathway during inflammation and may contribute to a range of neuroactive metabolites. In some contexts, 3HAA has been described as having antioxidant properties, though it can under others participate in oxidative processes.

Clinical and research relevance: 3HAA levels are measured in plasma, cerebrospinal fluid, and tissues in studies of neuroinflammation and neurodegenerative or psychiatric disorders. Alterations have been reported in conditions such as depression, Alzheimer's disease, and Huntington's disease, but findings are context-dependent and 3HAA is not a standalone diagnostic biomarker.