Alteration of mice L-tryptophan metabolism by the organophosphorous acid triester diazinon.
Diazinon [O,O-diethyl O-(2-isopropyl-6-methyl-4- pyrimidinyl)phosphorothioate] altered the formation of several L-tryptophan metabolites associated with the L-kynurenine pathway in mice. Liver kynurenine formamidase was inhibited almost completely by diazinon (10 mg/kg). The enzyme inhibition resulted in reduced L-kynurenine biosynthesis in livers with a concomitant accumulation of N-formyl-L-kynurenine. In contrast to the liver, plasma L-kynurenine increased up to 5-fold in diazinon-treated mice. Consequently, the urinary excretion of xanthurenic acid and kynurenic acid was raised 5- to 15-fold. The revelation of this novel mechanism of diazinon action is an important piece of information needed for a better understanding of the noncholinergic toxicity of organophosphorous acid triesters and methylcarbamates.
D000818:Animals; D005558:Arylformamidase / Q000037:antagonists & inhibitors; D003976:Diazinon / Q000633:toxicity*; D007736:Kynurenic Acid / Q000652:urine; D007737:Kynurenine / Q000031:analogs & derivatives / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008954:Models, Biological; D009243:NAD / Q000378:metabolism; D017378:Quinolinic Acid / Q000097:blood / Q000652:urine; D014364:Tryptophan / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000097:blood / Q000652:urine; D014977:Xanthurenates / Q000652:urine
D014977:Xanthurenates; D009243:NAD; C007772:N'-formylkynurenine; D007737:Kynurenine; C028330:xanthurenic acid; D014364:Tryptophan; D014366:Tryptophan Oxygenase; D005558:Arylformamidase; D017378:Quinolinic Acid; D007736:Kynurenic Acid; D003976:Diazinon