Cell metabolism in uremia

Abstract

We hypothesize that the metabolic abnormalities of uremia, including carbohydrate intolerance and impaired protein synthesis result from a disturbed balance between normally occurring positive and negative effectors of enzyme activity at the biomolecular level, superimposed on malnutrition. To test this hypothesis circulating polymorphonuclear leukocytes were used as an experimental cell model. Leukocytes were isolated from pre- and postdialysis blood of 31 adult uremic subjects undergoing chronic hemodialysis. A 6 hr dialysis was associated with significant (P< 0.05) increases in activities of the glycolytic enzymes pyruvic kinase, phosphofructokinase, and glucose-6-phosphate dehydrogenase. Protein synthesis (3H-leucine incorporation) also increased. Urea, added to the postdialysis leukocytes did not significantly affect the activities. Nor was the energy state of the cell significantly altered by dialysis, although levels of fructose 1–6 diphosphate and of 3 phosphoglycerate increased—suggesting an increased glycolytic flux at the step catalyzed by phosphofructokinase. Leukocyte amino acid levels increased suggesting decreased utilization for gluconeogenesis since both glycolysis and protein synthesis increased. Leukocyte phosphofructokinase activity and protein synthesis increased significantly only in patients having carbohydrate intolerance (predialysis blood glucose averaging 160 mg/dl), but not in those with normal glucose (averaging 108 mg/dl), although both groups had similar dialysis treatment. These observations support the hypothesis that imbalance of enzyme effectors at the molecular level, rather than dialyzable toxins, may account for the carbohydrate intolerance and impaired protein synthesis in uremia.