the 3HAO reaction is initiated by substrate binding, which induces closure of the active site. Oxygen then binds to the active-site iron. Transfer of an electron from the active-site iron to oxygen creates an oxygen radical, thereby facilitating the addition of both O atoms to 3-HANA and forming 2-amino-3-carboxymuconic 6-semialdehyde (ACMS), an active intermediate. ACMS then spontaneously cyclizes to form quinolinic acid
each monomer contains two iron binding sites. The catalytic iron is buried deep inside the beta-barrel with His51, Glu57, and His95 serving as ligands. The other iron site forms an FeS4 center close to the solvent surface in which the sulfur atoms are provided by Cys125, Cys128, Cys162, and Cys165. The two iron sites are separated by 24 A
it is possible that inhibition of 3-HAD may improve neurologic status through an increased production of kynurenic acid, a non-specific inhibitor of excitatory amino acid receptors and an inhibitor of quinolinic acid neurotoxicity
the inactivation results in the consumption of 2 equivalents of oxygen and the production of superoxide. The inhibitor stimulates the oxidation of the active site Fe(II) to the catalytically inactive Fe(III) oxidation state. The inactivated enzyme can be reactivated by treatment with DTT and FeI(II). The nhibitor does not form an adduct with the enzyme. Four conserved cysteines are oxidized to two disulfides (Cys125-Cys128 and Cys162-Cys165) during the inactivation reaction. These results are consistent with a mechanism in which the enzyme, complexed to the inhibitor and O2, generates superoxide which subsequently dissociates, leaving the inhibitor and the oxidized iron center at the active site
Changes in mouse liver and chicken embryo yolk sac membrane soluble proteins due to an organophosphorous insecticide (OPI) diazinon linked to several noncholinergic OPI effects in mice and chicken embryos.