Inactivation of Cu,Zn-superoxide dismutase by in vitro glycosylation and in erythrocytes of diabetic patients.

Purified bovine Cu,Zn-superoxide dismutase was nonenzymatically glycosylated in vitro at a rate proportional to incubation time (2 to 120 hrs) and glucose concentration (10 to 100 mM). Inverse correlation between glycosylation and the enzyme activity showed that increased glycosylation was accompanied with inactivation of the enzyme. Specific activities of glycosylated and non-glycosylated enzymes incubated with 100 mM glucose for 120 hrs were 1150 and 2860 units/mg protein, respectively. This indicates that nonenzymatic glycosylation declined the enzyme activity approximately to 40%. All these results were consistent with the in vivo studies that Cu,Zn-superoxide dismutase activity in erythrocytes of non-insulin dependent diabetic patients was inversely correlated with their plasma glucose. Inactivation of Cu,Zn-superoxide dismutase demonstrated by both in vitro and in vivo studies may be important for the development of diabetic complications, because the enzyme has a crucial role in protecting the body against the damaging effects of the superoxide radicals.