Increased susceptibility of carbamylated glutamate dehydrogenase to proteolysis

Glutamate dehydrogenase is very susceptible to carbamylation which results in loss of activity. The effect of a number of proteolytic enzymes (pronase, trypsin and chymotrypsin) on native and carbamylated glutamate dehydrogenase was tested. In all cases, the carbamylated enzyme was at least twice as susceptible to proteolysis as the native enzyme. Antibodies were prepared against glutamate dehydrogenase and carbamylated glutamate dehydrogenase; the carbamylated enzyme was antigenically indistinguishable from the native enzyme. Preliminary experiments indicate that the carbamylated glutamate dehydrogenase is taken up by ascites tumor cells while glutamate dehydrogenase is not. It seems possible that the effects described can be extrapolated to degradation by lysosomes and to other covalently modified enzymes.