Of the major components of the
kynurenine pathway for the oxidative metabolism of
tryptophan, most attention has focussed on the
N-methyl-D-aspartate (
NMDA) receptor agonist
quinolinic acid, and the
glutamate receptor blocker
kynurenic acid. However, there is increasing evidence that the redox-active compound
3-hydroxyanthranilic acid may also have potent actions on cell function in the nervous and immune systems, and recent clinical data show marked changes in the levels of this compound, associated with changes in
anthranilic acid levels, in patients with a range of neurological and other disorders including
osteoporosis,
chronic brain injury,
Huntington's disease,
coronary heart disease,
thoracic disease,
stroke and depression. In most cases, there is a decrease in
3-hydroxyanthranilic acid levels and an increase in
anthranilic acid levels. In this paper, we summarise the range of data obtained to date, and hypothesise that the levels of
3-hydroxyanthranilic acid or the ratio of
3-hydroxyanthranilic acid to
anthranilic acid levels, may contribute to disorders with an inflammatory component, and may represent a novel marker for the assessment of
inflammation and its progression. Data are presented which suggest that the ratio between these two compounds is not a simple determinant of neuronal viability. Finally, a hypothesis is presented to account for the development of the observed changes in
3-hydroxyanthranilic acid and
anthranilate levels in
inflammation and it is suggested that the change of the 3HAA:AA ratio, particularly in the brain, could possibly be a protective response to limit primary and secondary damage.