3-HYDROXYANTHRANILATE OXIDASE

Figure 8.4. Pathways of tryptophan metaholism. Tryptophan dioxygenase, EC 1.13.11.11 formylkynurenine formamidase, EC 3.5.1.9 kynurenine hydroxylase, EC 1.14.13.9 kynureninase, EC 3.7.1.3 3-hydroxyanthranilate oxidase, EC 1.10.3.5 picolinate carboxylase, EC 4.1.1.45 kynurenine oxoglutarate aminotransferase, EC 2.6.1.7 kynurenine glyoxylate aminotransferase, 2.6.1.63 tryptophan hydroxylase, EC 1.14.16.4 and 5-hydroxytryptophan decarboxylase, EC 4.1.1.26. Relative molecular masses (Mr) tryptophan, 204.2 serotonin, 176.2 kynurenine, 208.2 3-hydroxykynurenine, 223.2 kynurenic acid, 189.2 xanthurenic acid, 205.2 and quinolinic acid 167.1. CoA, coenzyme A.

Indirect evidence for the existence of such an enzyme arose from the observation [30] that in vitro administration of anthranilic acid to rat neurons causes an increase in intracellular HA concentration. However, that study did not pay due attention to the earlier observation [31], that anthranilic acid is an effective inhibitor (Ki 40 pM) of the enzyme, devoted to HA oxidation, 3-hydroxyanthranilate oxidase (dioxygenase). Therefore, the increase in HA concentration could well be due to an inhibitory effect of anthranilic acid towards the further catabolism of HA, and not to a direct conversion of anthranilic acid to HA. 

An enzyme catalyzing the oxidation of 3-hydroxyan-thranilic acid was found in liver and kidney. The 3-hydroxyanthranilic oxidase has been partially purified from beef liver, and requirements for ferrous ions and sulfhydryl groups have been demonstrated. 

Hydroxyanthranilate oxidase functions during intermediary metabolism of tiyptophan, as depicted in Figure 4. It transforms 3-hydroxyanthranilic acid into a substance, not raitirely characterized, from which quinolinic, picolinic, and nicotinic adds arise (75,76, 188,346,348,449,540,649,650,776,833, and the reviews 182,312,538). The enzyme occurs in pig, ox and rat liver and kidney, but not in other organs (348,600,650,666). 

Tracer studies of the fate of oxygen consumed during protocate-chuic acid cleavage have not been carried ocit, but because of oxygen stoichiometry, dependence of the enzyme upon ferrous ions, and resemblance of the over-all reaction to those catalyzed by pyrocate-chase, homogentisate oxidase, and 3-hydroxyanthranilate oxidase (compare 171), it is reasonable to classify protocatechuic acid oxidase as an oxygen transferase. 

Hydroxyanthranilic oxidase is a relatively stable constituent of those organs in which it formed. Gross alterations in the physiological state of... 

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