3-Hydroxyanthranilate oxidation

Reported redox potentials of laccases are lower than those of non-phenolic compounds, and therefore these enzymes cannot oxidize such substances [7]. However, it has been shown that in the presence of small molecules capable to act as electron transfer mediators, laccases are also able to oxidize non-phenolic structures [68, 69]. As part of their metabolism, WRF can produce several metabolites that play this role of laccase mediators. They include compounds such as /V-hvdi oxvacetan i I ide (NHA), /V-(4-cyanophenyl)acetohydroxamic acid (NCPA), 3-hydroxyanthranilate, syringaldehyde, 2,2 -azino-bis(3-ethylben-zothiazoline-6-sulfonic acid) (ABTS), 2,6-dimethoxyphenol (DMP), violuric acid, 1-hydroxybenzotriazole (HBT), 2,2,6,6-tetramethylpipperidin-iV-oxide radical and acetovanillone, and by expanding the range of compounds that can be oxidized, their presence enhances the degradation of pollutants [3]. 

Precursors in the biosynthesis of niacin In animals and bacteria, tryptophan and in plants, glycerol and succinic acid. Intermediates in the synthesis include kynurenine, hydroxyanthranilic acid, and quinolinic acid. In animals, the niacin storage sites are liver, heart, and muscle. Niacin supplements are prepared commercially by (1) Hydrolysis of 3-cyanopyndine or (2) oxidation of nicotine, quinoltne, or collidine. 

In the catabolic pathway of tryptophan there are a number of reactions, starting with the oxidation product of 3-hydroxyanthranilate, that involve conjugated enamines, the... 

Kynureninase is involved in the oxidative metabolism of tryptophan. It catalyzes the conversion of L-kynurenine to anthranilic acid. The enzyme also converts L-3-hydroxykyneurenine to 3-hydroxyanthranilic acid. The latter compound has a high fluorescence, which is the basis for detection in this assay. 

Ogino and Ichihara (02) reported in 1957 the isolation in pure form of 5-hydroxyanthranilic acid and anthranilic acid from urine of patients with senile cataract. Bromine oxidation of 5-hydroxyanthranilic yielded quinoniminecarboxylic acid, which showed cataractogenic activity when injected in scorbutic guinea pigs. 

In independent studies, Aprison et al. (A7) found among tryptophan metabolites that 3-hydroxyanthranilic acid was capable of inhibiting the oxidation of N,N-dimethyl-p-phenylendiamine by purified ceruloplasmin and serum oxidase. 

Formation of Qa via aerobic degradation ofTrp (Kyn pathway) includes five enzymatic steps (1) oxidation of Trp to N-formyl kynurenine (FKyn) by Trp 2,3-dioxygenase (TRDOX), (2) deformylation of FKyn by kynurenine formamidase (KYNFA), (3) oxidation of Kyn to 3-hydroxykynurenine (HKyn) by kynurenine 3-monooxygenase (KYNOX), (4) conversion of HKyn into 3-hydroxyanthranilate (HAnt) by kynureninase (KYNSE), and (5) oxidation of HAnt by 3-hydroxyanthranilate 3,4-dioxygenase (HADOX) to a-amino-/3-carboxymuconic semialdehyde (ACMS) followed by its spontaneous cyclization to Qa (Scheme 2). This pathway and all respective... 

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. 

Fig. (2). The (auto)oxidation pathway of 3-hydroxyanthranilic acid, leading to cinnabarinic acid...

Fig. (4).The quinonoid compound, arising from 3-hydroxyanthranilic acid (auto)oxidation...

Fig. (6). Oxidative coupling of lysine and cysteine to 3-hydroxyanthranilic acid...

Fig. (7). The tricyclic lactone, arising from oxidative coupling between tyrosine and 3-hydroxyanthranilic acid...

In several instances polymeric substances arise during the transformation of secondary products, such as polymeric carbohydrates (D 1.4.1), humic acid-like polyphenols (D 3.3.1), rubber (D 6), sporopoUenins (D 6.5), polymeric products derived from 3-hydroxyanthranilic acid (D 8.4.1), melanins (D 22.1.3), lignins (D 22.2.3), and muramin (D 23.4). Many of these compounds are formed by oxidative polymerization catalyzed by phenoloxidases (C 2.3.1) and peroxidase... 

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. 

In the presence of O2, the oxidase opens the ring of 3-hydroxyanthranilate and oxidizes both the carbon bound to the hydroxyl group to yield a carboxyl group and the adjacent carbon to yield an aldehyde group. 2-Acroleyl-3-aminofumarate is the final product of the reaction. The nitrogen is then incorporated into a heterocyclic ring of quinolinic acid (or pyridine-2,3-... 

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