Formyl kynurenine

Griffiths, H.R, Lunec, J. and Blake, D.R. (1992). Oxygen radical-induced fluorescence in proteins identification of the fluorescent tryptophan metabolite N formyl kynurenine as a biological index of radical damage. Amino Acids 3, 183-194. 

A previous study of the reaction of ozone with lysoz3mie dissolved in anhydrous formic acid gave rise to the conclusion that the only amino acid residues affected in the early stages of the reaction were the tryptophan residues 108 and 111 ( ). Conversion of these residues to N -formyl-kynurenine did not cause loss in enzyme activity. Imoto et al. (7) have pointed out that this result is anomalous since modifications of tryptophan 108 (e.g. with iodine) normally causes inactivation. 

Catabolism of tyrosine and tryptophan begins with oxygen-requiring steps. The tyrosine catabolic pathway, shown at the end of this chapter, results in the formation of fumaric acid and acetoaceticacid, Iryptophan catabolism commences with the reaction catalyzed by tryptophan-2,3-dioxygenase. This enzyme catalyzes conversion of the amino acid to N-formyl-kynurenine The enzyme requires iron and copper and thus is a metalloenzyme. The final products of the pathway are acetoacetyl-CoA, acetyl-Co A, formic add, four molecules of carbon dioxide, and two ammonium ions One of the intermediates of tryptophan catabolism, a-amino-P-carboxyrnuconic-6-semialdchydc, can be diverted from complete oxidation, and used for the synthesis of NAD (see Niacin in Chapter 9). 

Walrant, R and Santus, R., N-formyl-kynurenine, a tryptophan photooxidation product, as a photodynamic sensitizer, Photochem. Photobiol., 411, 1974, 1974. 

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... 

L-Tryptophan is degraded via oxidative cleavage of the C-2,C-3 bond, to give A-formyl-kynurenine, as shown in Figure 25. Tryptophan 2,3-dioxygenase (TDO), found in mammals and bacteria, is selective for cleavage of tryptophan, whereas indoleamine 2,3-dioxygenase (IDO), found only in mammals, is able to cleave other... 

Tryptophan N-formyl kynurenine kynurenine hydroxy tryptophans (55,78)... 

Wool photodiscolouration is also a problem and is normally associated with the photoproducts of tryptophan. These have been identified as N-formyl-kynurenine, k]murenine, tryptamine and oxyindolylalanine. Short wavelength blue light has been found to effectively photobleach the yellowing of wool. These processes have been discussed in detail. ... 

The discovery that formylkynurenine is formed by an oxygenation reaction, with the introduction of two atoms of oi gen into tryptophan eliminates the posrability or need of an oxidation product contaming only one atom of oigrgen. Hie Ot must be introduced in a single step into the tryptophan giving a product which immediately rearranges to formyl-kynurenine. This makes a hydroxy intermediate improbable and unnecessary. 

Tryptophan oxidation in liver has been found to be adaptive (36,43,44)-Administration of the amino acid to rabbits or rats results in an approximately tenfold increase in the amount of the tryptophan oxidizing system. This rise in enzyme occurs some 6 hr after the administration of a single dose of tryptophan, and then rapidly decreases. This increase appears to be due to true synthesis, since ethionine will inhibit the adaptive formation of the enzyme (46). It is of interest that the only step in the conversion of tryptophan to nicotinic acid which is adaptive is the oxidation to formyl-kynurenine (43),. This is in contrast to the finding in bacteria, where a number of the enzymes in the tryptophan oxidation sequence have been found to be adaptive (43). 

There is another type of oxidative process which might be classified among the energizing reactions. The first step in the oxidation of tryptophan to formyl kynurenine is catalyzed by a peroxidase-H202 system.Aerobic oxidases such as xanthine oxidase, d-amino acid oxidase, and urico-oxidase produce H2O2 during oxidation of their respective... 

The most widely accepted theory of wool yellowing proposes the photooxidation of the tryptophan groups (4.130) to yellow coloured N-formyl-kynurenine (4.133) and kynurenine (4.134) [964, 1576] ... 

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. 

Although Savige 338) earlier found no reaction between formyl-kynurenine and ammonia in the very dilute aqueous ammonia used in the photoconversion of tryptophan to (80), he has since found that formylkynurenine on treatment with 2N aqueous ammonia in... 

Previero, A., M. A. Coletti-Previero, and P. JoLLfes Nonenzymatic Cleavage of Tryptophyl Peptide Bonds in Peptides and Proteins. I. Cleavage of C-trypto-phyl Peptide Bonds in Model Peptides through their Conversion into N -Formyl-kynurenine Derivatives. Biochem. Biophys. Res. Commun. 22, 17-21 (1966). 

Walrant, P., and R. Santus Ultraviolet and N-Formyl-kynurenine Sensitized Photoinactivation of Bovine Carbonic Anhydrase an Internal Photodinamic Effect. Photochem. Photobiol. 20, 455-460 (1974). 

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