Disease relevance of N-formylkynurenine

• The interferon (IFN)-gamma-mediated induction of indoleamine 2,3-dioxygenase (IDO) enzyme, which converts tryptophan into N-formylkynurenine, has been implicated in the inhibition of intracellular pathogens, e.g. Toxoplasma gondii and Chlamydia psittaci, and in the antiproliferative effect of IFN-gamma on tumor cells [1].
• Of these, five were derived from tryptophan; namely hydroxytryptophan, N-formylkynurenine, kynurenine, residues consistent with the dehydration of kynurenine, and hydroxykynurenine, while three were derived from tyrosine; namely dihydroxyphenylalanine, dityrosine, and a cross-linked residue consistent with a hydroxylated dityrosine residue [2].

Psychiatry related information on N-formylkynurenine

• In CSF protein, the concentrations of 3-nitrotyrosine, N(epsilon)-carboxymethyl-lysine, 3-deoxyglucosone-derived hydroimidazolone and N-formylkynurenine residues were increased in subjects with Alzheimer's disease [3].

High impact information on N-formylkynurenine

• Liver cytosols from several mammalian species exhibited a significant N-formylating activity toward the arylamines in the presence of N-formyl-L-kynurenine and N-acetylating activity in the presence of acetyl-CoA [4].
• The formation of N-formylkynurenine by dioxygenation of tryptophan was detected in peptides from rice leaf and potato tuber mitochondria [5].
• Results show that a peptide region (31-36) of hSOD1 containing the Trp-32 residue (VWGSIK) is oxidatively modified to the N-formylkynurenine (NFK)- and kynurenine (Kyn)-containing peptides (V(NFK)GSIK) and (V(Kyn)GSIK) during HCO(-)-dependent peroxidase activity of hSOD1 [6].
• In control gerbils, 22% of L-kynurenine in brain was derived via local synthesis from L-tryptophan/formylkynurenine versus 78% from L-kynurenine from blood [7].
• Indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme in the L-tryptophan-kynurenine pathway, which converts an essential amino acid, L-tryptophan, to N-formylkynurenine [8].

Biological context of N-formylkynurenine

• By photoirradiation of the enzyme with the reagent, which can occupy a binding site of the enzyme, a tryptophan residue in the vicinity of the active site was oxidized to N-formylkynurenine [9].
• Preferential acid-catalyzed hydrolysis of the formamide linkage of N'-formylkynurenine in frozen solution [10].
• The formamidase obtained has substrate specificity for o-formylaminoacetophenone only and could not hydrolyze formylkynurenine [11].

Anatomical context of N-formylkynurenine

• Addition of kynurenine or N-formylkynurenine to rickettsia-infected human fibroblasts at concentrations four times the usual tryptophan concentration did not inhibit growth of R. prowazekii [12].

Associations of N-formylkynurenine with other chemical compounds

• In NFK 59-RNase T1, both N'-formylkynurenine and tyrosine showed almost the same fluorescence behavior during titration, which was characterized by two transitions between pH 3 and 8 in each titration curve [13].
• KFase was isolated here from mouse liver cytosol by (NH4)2SO4 precipitation and three FPLC steps (resulting in 221-fold increase in specific activity for N-formyl-L-kynurenine hydrolysis) followed by conversion to [3H]diethylphosphoryl-KFase and finally isolation by C4 reverse-phase high-performance liquid chromatography [14].
• Kynurenine formamidase (KFase) (EC 3.5.1.9) hydrolyzes N-formyl-L-kynurenine, an obligatory step in the conversion of tryptophan to nicotinic acid [14].

Gene context of N-formylkynurenine

• Trp 187 of the constant fragment of a type lambda immunoglobulin light chain, Trp 59 of ribonuclease T1, and Trp 62 of hen egg white lysozyme were oxidized specifically by ozone to N'-formylkynurenine or kynurenine [15].
• N-Formylkynurenine increased from an initial value of 0.21 to 1.67 mol/mol apo B within 5 h [16].
• Expressed AFMID showed high activity, 42+/-1 micromol/min/mg protein, for its natural substrate, N-formyl-l-kynurenine [17].
• Subcutaneous administration of CoCl2, a well recognized inhibitor of hepatic heme synthesis, to rats results in the functional stimulation of total (holo- + apo) tryptophan 2,3 dioxygenase (TDO), a hemoprotein and the key rate-limiting enzyme in the oxidative metabolism of tryptophan to formylkynurenine [18].

Analytical, diagnostic and therapeutic context of N-formylkynurenine

• Cells treated with Hu-rIFN-gamma also degraded L-[3H]tryptophan to catabolites that cochromatographed with N-formylkynurenine and kynurenine as measured by high-performance liquid chromatography [19].
• A pulse-radiolysis study of the reaction of hydrated electrons with N'-formylkynurenine and related compounds: electron-transfer reactions with nucleic acid components [20].

References