title: Protein degradation in metabolic and nutritional disorders.
abstract: The increased protein degradation associated with diabetes appears to be different in many respects from protein catabolism in normal, well-nourished cells. In all normal eukaryotic cells examined, degradation of cytosolic proteins exhibits several striking features. Large 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 are degraded more rapidly than non-glycoproteins. Furthermore, a general correlation exists between protein half-life in vivo and susceptibility to proteolytic attack in vitro. In streptozotocin-diabetic rats the relationships between degradative rate and protein size, net charge, and carbohydrate content are absent or markedly reduced among cytosolic proteins of the liver. However, the correlation between protein half-life and susceptibility to proteinase in vitro is unaltered. Therefore, the enhanced protein degradation in diabetes shows little or no selectivity towards large, acidic, glycoproteins but does show specificity for proteins than tend to be sensitive to proteinases. Similar studies using other tissues from diabetic rats are reported and general characteristics of the enhanced liver protein catabolism in starvation and hyperthyroidism are briefly discussed. The biochemical reasons for the increased protein catabolism in diabetes are unclear although several possible explanations are presented. The enhanced breakdown is probably not due to cellular proteins becoming more proteinase sensitive in diabetes since experiments with a variety of endoproteinases including pronase, chymotrypsin, pepsin, and lysosomal cathepsins have failed to demonstrate more rapid digestion of liver proteins from diabetic animals.
mesh_terms: D000818:Animals; D003600:Cytosol / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D006207:Half-Life; D066298:In Vitro Techniques; D007328:Insulin / Q000502:physiology; D008099:Liver / Q000378:metabolism; D009748:Nutrition Disorders / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D051381:Rats
chemical_list: D007328:Insulin; D011506:Proteins; D010450:Endopeptidases