Studies with tryptophan metabolites in vitro. effect of zinc, manganese, copper and cobalt ions on kynurenine hydrolase and kynurenine aminotransferase in normal mouse liver

The possible mechanisms by which increasing concentrations of Zn 2+, Mn 2+, Cu 2+, or Co 2+ may affect the vitamin B 6-dependent enzymes kynurenine hydrolase and kynurenine aminotransferase. were studied in normal mouse liver homogenates. It was found that Zn 2+ inhibited kynurenine hydrolase. whereas Mn 2+ activated this enzyme, but both Zn 2+ and Mn 2+ activated kynurenine aminotransferase. Co 2+ and Cu 2+ inhibited both enzymes. This inhibition is attributed to the blocking and inactivation of the -SH groups of these enzymes and may be due to the adequate sequence of the -SH groups in both enzymes for Cu 2+ or Co 2+ action. This is in contrast to the inadequate sequence of these groups in kynurenine aminotransferase for Zn 2+ action. The decreasing order by which these metal ions inhibit (a) kynurenine hydrolase is Cu 2+ > Co 2+ > Zn 2+, and (b) kynurenine aminotransferase is Cu 2+ > Co 2+. The decreasing order of the per cent activation of the aminotransferase enzyme is Mn 2+ > Zn 2+. These decreasing orders fall into a more reasonable order approximating the order of complex stability of these metal ions.