Kynurenine formamidase

Eto M, Seifert J, Engel JL, et al. 1980. Organophosphorus and methylcarbamate teratogens structural requirements for inducing embryonic abnormalities in chickens and kynurenine formamidase inhibition in mouse liver. Toxicol Appl Pharmacol 54(l) 20-30. 

Seifert J, Casida JE. 1978. Relation of yolk sac membrane kynurenine formamidase inhibition to certain teratogenic effects of organophosphorus insecticides and of carbaryl and eserine in chicken embryos. Biochem Pharmacol 27 2611-15. 

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... 

Katz (70) and Brown et al. (19,71) demonstrated the presence of two forms of kynurenine formamidase in S. parvulus. Kynurenine formamidase catalyzes the conver-... 

Kynurenine formamidase catalyzes the hydrolysis of formylkynurenine. A variety of aromatic forma-mides will react, but the enzyme is more active with its natural than with the synthetic substrates. The product of the reaction, kynurenine, may then either be hydroxylated or decarboxylated. 

Kynurenine Formylase. Hydrolysis of formylkynurenine to kynurenine is catalyzed in liver preparations by an enzyme (formylase or kynurenine formamidase) with rather low specificity for aromatic formamides. The reaction with formylkynurenine, however, is faster than that with any analogs. A very similar enzyme has been obtained from Neurospora. In contrast, an enzyme from insects does not hydrolyze formylanthranilic acid, a model substrate for formylase from other sources, or other analo-... 

The experiments discussed above on the biosynthesis of a pseudan have also shown that kynurenic acid is not the precursor of the 2-alkylquinolin-4(lH)-ones. Based on the putative function of the genes of the qbs operons (176), a pathway was proposed for the biosynthesis of kynurenic acid (I), xanthurenic acid [10(8)], and quinolobactin [IO(8) j in Pseudomonas fluorescens ATCC 17400 (Scheme 5). The first step, the oxidation of tryptophan to N-formylkynurenine, is likely to be catalyzed by the enzyme tryptophan 2,3-dioxygenase (TDO) (QbsF), which is a heme-dependent enzyme. The second step, the deformylation of N-formyl-kynurenine to L-kynurenine is catalyzed by kynurenine formamidase (KFA). The product of qbsH, a metal-dependent hydrolase found also in other bacterial genomes, is the likely candidate. 

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