General characteristics of protein degradation in diabetes and starvation.

The enhanced protein degradation associated with diabetes and starvation is fundamentally different from normal protein catabolism. In normal eukaryotic cells large molecular weight proteins tend to be degraded more rapidly than small proteins, acidic proteins tend to be degraded more rapidly than neutral or basic proteins, and glycoproteins tend to be degraded more rapidly than nonglycoproteins. All three of these general correlations are absent or markedly reduced in liver and muscle of diabetic and starved rats. In contrast, the correlations between proteins size and half-life, between protein net charge and half-life, and between protein carbohydrate content and half-life are not affected in brain of diabetic or starved animals. These results suggest that diabetes and starvation alter the general characteristics of intracellular protein degradation in target tissues of insulin. Degradation of serum proteins is also affected in diabetes and starvation. In normal animals a general correlation exists between isoelectric points of serum proteins and their degradative rates. This relationship is abolished in diabetes and starvation, as it is among liver and muscle proteins. The implications of our findings are discussed with regard to possible mechanisms of the enhanced protein breakdown.