Inhibition of glutamate dehydrogenase by bilirubin.

Abstract

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 accelerated the inhibitory effect. Bilirubin inhibition was reversible in the presence of zinc ion at 2×10−2M under the present experimental conditions. Three modes of inhibition by bilirubin were suggested; 1) zinc chelation, 2) denaturation by detergent action, and 3) competition with the pyridinium ring of NAD at the binding site.