Inhibition of Glutamate Dehydrogenase by Bilirubin

Bilirubin inhibition of crystalline beef liver glutamate dehydrogenase [EC 1.4.1.3] was demonstrated. Bilirubin glucuronide was a more potent inhibitor than free •bulirubin, and albumin bound bilirubin had the least inhibitory effect on the enzyme. Bilirubin glucuronide was possibly contaminated by bile salts, which may have ac-celerated the inhibitory effect Bilirubin inhibition was reversible in the presence of zinc ion at 2 x 10" * M under the present experimental conditions. Three modes of inhibition by bilirubin were suggested; 1) zinc chelation, 2) denaturation by deter-gent action, and 3) competition with the pyridinium ring of NAD at the binding site. Numerous reports have appeared concerning allosteric regulation of some metabolites on glutamate dehydrogenase (GDH) [EC 1.4.1. 3] as inhibitors or activators. Among nucleotides, ADP enhances the enzyme activity, while GTP disaggregates the enzyme unit that is cata