3-hydroxyanthranilate 3,4-dioxygenase

HAAO (3-hydroxyanthranilate 3,4-dioxygenase) is a 286-amino-acid enzyme that catalyzes the oxidative ring opening of 3-hydroxyanthranilate to 2-amino-3-carboxymuconate semialdehyde, a precursor in the kynurenine pathway that spontaneously cyclizes to quinolinate (UniProt: P46952). The enzyme is involved in tryptophan catabolism and NAD biosynthesis. HAAO variants are associated with vertebral, cardiac, renal, and limb defects syndrome 1 (VCRL1), a rare autosomal recessive developmental disorder, though this represents a congenital rather than neurodegenerative phenotype.

In Alzheimer's disease, HAAO is upregulated in post-mortem human brain tissue compared to age-matched controls (Chaparral AD proteomics). The mean log2 fold-change is 0.4636 across the measured subcellular fractions from TMT-labeled tandem mass spectrometry analysis. This elevation suggests potential dysregulation of kynurenine pathway metabolism in AD pathology, though the functional consequence of increased HAAO expression in neurodegeneration remains to be elucidated.