Disease relevance of Afmid

• Because of the potential of the majority of organophosphorous acid triesters and methylcarbamates to inhibit kynurenine formamidase, this novel noncholinergic mechanism warrants consideration in assessment of organophosphorous and methylcarbamate toxicity in occupational and accidental exposures [1].
• The cDNA sequence previously identified for mouse liver AFMID (AF399717) (MW 34229) was cloned and expressed in Escherichia coli [2].

High impact information on Afmid

• The binding site for the growth-regulated transcription factor E2F is beneficial for TK promoter activity but not required for KF expression [3].
• Similarly, TK gene activation by interleukin-2 is linked to histone hyperacetylation, whereas KF expression correlates with reduced histone acetylation [3].
• This gene encodes kynurenine formamidase (KF), an enzyme of the tryptophan metabolism [3].
• Whereas the TK gene is induced upon interleukin-2-mediated activation of resting T cells, the KF gene becomes simultaneously repressed [3].
• Our results demonstrated that in various tissues, N-formylkynurenine produced by the dioxygenase from tryptophan was rapidly hydrolyzed into kynurenine by a kynurenine formamidase, but it was not further metabolized [4].

Biological context of Afmid

• In wild-type (WT) mice, Afmid-specific activity (as measured by formyl-kynurenine hydrolysis) was 2-fold higher in the liver than in the kidney [5].
• Effect of arylformamidase (kynurenine formamidase) gene inactivation in mice on enzymatic activity, kynurenine pathway metabolites and phenotype [5].

Anatomical context of Afmid

• Afmid/Tk -deficient mice are known to develop sclerosis of glomeruli and to have an abnormal immune system [5].

Associations of Afmid with chemical compounds

• On this basis, the most significant function of the kynurenine pathway and Afmid in mice may be in eliminating toxic metabolites and to a lesser extent in providing intermediates for other processes [5].
• Plasma concentrations of formyl-kynurenine, kynurenine, and kynurenic acid were elevated in KO mice (but not HZ mice) relative to WT mice, further suggesting that there must be enzymes other than Afmid (possibly in the kidney) capable of metabolizing formyl-kynurenine into kynurenine [5].
• Kynurenine formamidase (KFase) (EC 3.5.1.9) hydrolyzes N-formyl-L-kynurenine, an obligatory step in the conversion of tryptophan to nicotinic acid [6].
• Liver kynurenine formamidase was inhibited almost completely by diazinon (10 mg/kg) [7].
• Kynurenine formamidase inhibition as a possible mechanism for certain teratogenic effects of organophosphorus and methylcarbamate insecticides in chicken embryos [8].

Other interactions of Afmid

• However, there was 13% residual formyl-kynurenine hydrolysis in the kidney of KO mice, suggesting the existence of a formamidase other than Afmid [5].
• Kynurenine formamidase: determination of primary structure and modeling-based prediction of tertiary structure and catalytic triad [6].

Analytical, diagnostic and therapeutic context of Afmid

• Two enzymic forms of kynurenine formamidase (EC 3.5.1.9) from Drosophila melanogaster were separated and partially purified by pH fractionation, (NH4) 2SO4 fractionation and Sephadex G-75 gel filtration [9].

References