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. 2010:3:51-9.
doi: 10.4137/ijtr.s4282. Epub 2010 Jun 10.

On the Biological Importance of the 3-hydroxyanthranilic Acid: Anthranilic Acid Ratio

L Gail Darlington  1 , Caroline M Forrest, Gillian M Mackay, Robert A Smith, Andrew J Smith, Nicholas Stoy, Trevor W Stone
Affiliations

On the Biological Importance of the 3-hydroxyanthranilic Acid: Anthranilic Acid Ratio

L Gail Darlington et al. Int J Tryptophan Res. 2010.

Abstract

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.

Keywords: 3-hydroxyanthranilic acid; Huntington’s disease; anthranilic acid; inflammation; kynurenines; stroke.

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Figures

Figure 1.
Figure 1.
Neurotoxic effects of 3-hydroxyanthranilic acid/anthranilic acid combinations. The effects on neuronal viability (cerebellar granule neurons) of different ratios of AA and 3-hydroxyanthranilic acid. In these selected examples of a wider series, 3-hydroxyanthranilic acid (3HAA) at a concentration of 100 μM is illustrated in combination with anthranilic acid (AA) at concentrations ranging from 0 to 1000 μM. Although there is a clear trend for the higher concentration to increase 3-hydroxyanthranilic acid—induced neurotoxicity, lower concentrations tend to reduce the damage, although none reached statistical significance in this series. Although the range of concentrations illustrated showed no significant interaction, lower concentrations which were closer to those measured in human blood, also showed no apparent interaction in this system. No clear, significant interactions were seen when the ratios of 3HAA:AA were reversed. The number of experiments is indicated within each column. (Adapted from A J Smith, PhD thesis, University of Glasgow, 2008).
Figure 2.
Figure 2.
Key elements of the kynurenine pathway.
See this image and copyright information in PMC

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