Hydroxyanthranilate dioxygenase

Hydroxyanthranilate dioxygenase (E.C. 1.13.11.6 - 3-Hydroxy-anthranilate oxygen 3,4-oxidoreductase (decyclizing)... 

Muraki T, M Taki, Y Hasegawa, H Iwaki, PCK Lau (2003) Prokaryotic homologues of the eukaryotic 3-hydroxyanthranilate 3,4-dioxygenase and 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase in the 2-nitrobenzoate degradation pathway of Pseudomonas fluorescens strain KU-7. Appl Environ Microbiol 69 1564-1572. 

Malherbe P, C Kohler, M Da Prada, G Lang, V Kiefer, R Schwarcz, H-W Lahm, AM Cesura (1994) Molecular cloning and functional expression of human 3-hydroxyanthranilic-acid dioxygenase. J Biol Chem 269 13792-13979. 

Cleavage of 3-hydroxykynurenine by kynureninase (step g, Fig. 25-11) forms 3-hydroxyanthranilate, which is opened under the action of another dioxygenase (step h) with eventual degradation to acetyl-CoA, as indicated. In insects the reactive 3-hydroxyanthranilate is utilized in "tanning" reactions, e.g., coupling to tyrosine residues to toughen insect cuticles and walls of cocoons.214... 

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.

Linderberg M, Hellberg S, Bjork S, Gotthammer B, Hogberg T, Persson K, Schwarcz R, Luthman J, Jo-hansson R (1999) Synthesis and QSAR of substituted 3-hydroxyanthranilic acid derivatives as inhibitors of 3-hydroxyanthranilic acid dioxygenase (3-HAO). Eur J Med Chem 34 729-744... 

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. 244. Degradation of L-tryptophan via kynurenine and 3-hydroxyanthranilic acid 1 Tryptophan 2,3-dioxygenase (tryptophan pyrrolase, C 2.5) 2 formamidase 3 kynurenine 3-monooxygenase 4 kynureninase 5 3-hydroxyanthranilate 3,4-dioxygenase 6 aminocarhoxy-muconate semialdehyde decarboxylase 7 aminomuconate semialdehyde dehydrogenase 8 0x0-glutarate dehydrogenase system 9 spontaneous cyclization...

Degradation of L-tryptophan in most organisms proceeds via L-kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxyanthranilic acid and quinolinic acid to acetyl Co A and CO2 (Fig. 244). Anthranilic acid formed as an intermediate may be recycled to L-tryptophan (see above). The ring of 3-hydroxyanthranilic acid is cleaved by a dioxygenase (C 2.5). The x-amino-/3-carboxymuconic acid-e-semialdehyde formed either undergoes a cis trans isomerization of the Zl -double bond and cyclization to quinolinic acid, a compound synthesized in microorganisms and plants from aspartic acid and D-glyceraldehyde-3-phosphate (D 16.2). On the other hand o -amino-/3-carboxymuconic acid-e-aldehyde may be de-carboxylated and is then the immediate precursor of NH3, acetic acid and COg. 

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