Enzyme anthranilate 1,2-dioxygenase

Samples of (3R)- and (3S)-[3- Hi]tryptophans 331 have been converted to the corresponding kynurenines 336 using the enzymes tryptophan dioxygenase (EC 1.13.11.11) and formylkynurenine formamidase (EC 3.5.1.9). These have been used to investigate the fission of kynurenine 336 to anthranilic acid 300 and alanine 337 in H20 (337) (Scheme 85). Conversion of the alanine to acetate and assessment of sense of chirality indicated that... 

An enzymatic pathway for indole degradation was found in A. niger, inducible by the substrate within a 5-h period during growth. Among the enzymes found, anthranilate hydroxylase, N-formylanthranilate deformylase, 2,3-dihydroxybenzoate decarboxylase, and catechol dioxygenase were isolated, and their activities were demonstrated in a cell-free system [342],... 

Decarbonilyzing (CO removal) enzyme 1H-3-OH-4-oxoQN-2, 4-dioxygenase BDN through the anthranilic acid pathway ... 

This enzyme [EC 1.14.13.35], also referred to as anthranilate 3-monooxygenase (deaminating) and anthranilate 2,3-dioxygenase (a transferred entry, formerly EC 1.14.12.2), catalyzes the reaction of anthranilate with NADPH and dioxygen to generate 2,3-dihydroxybenzo-... 

Returning to the major tryptophan catabolic pathway, marked by green arrows in Fig. 25-11, formate is removed hydrolytically (step c) from the product of tryptophan dioxygenase action to form kynurenine, a compound that is acted upon by a number of enzymes. Kynureninase (Eq. 14-35) cleaves the compound to anthranilate and alanine (step d), while transamination leads to the cyclic kynurenic acid (step e). Hie latter is dehydroxylated in an unusual reaction to quinaldic acid, a prominent urinary excretion product. 

Similar reactions were reported for the broad-substrate-specific benzoate dioxygenase of Rhodococcus sp. strain 19070[2G. Recombinant E. coli containing this enzyme transform benzoate and anthranilate to catechol and 2-hydro-l,2-dihydroxybenzoate, respectively. 

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. 

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