Functional and metabolic studies on red blood cell sodium transport in chronic uremia.
Red blood cells from 7 out of 13 patients with chronic uremia were found to have increased intracellular concentrations of sodium associated with a reversible inhibition of ouabain-sensitive Na efflux when incubated in control plasma. Although mean Na-K-ATPase activity of RBC hemolysates was only moderately decreased (21.8 +/- 1.5 vs. 26.5 +/- 1.8 nmol Pi/mg protein/h), enzyme kinetics revealed a significant increase in KmATP values for this enzyme in uremic RBCs (1.01 +/- 0.1 vs. 0.58 +/- 0.03; p less than 0.001) which was closely correlated to serum creatinine concentration (r = 0.9034). While aerobic glycolysis was unaltered, an increase in glucose-6-phosphate dehydrogenase activity was observed, i.e. the enzyme initiating the pentose-phosphate cycle. In addition, intracellular ATP concentrations of uremic RBCs were significantly higher than ATP concentrations of control RBCs (2.13 +/- 0.22 vs. 1.32 +/- 0.06 mmol/l RBC; p less than 0.01). These data suggest that high intracellular concentrations of Na and ATP in uremic RBCs partially result from a competitive reversible inhibition of the transport ATPase by uremic toxins.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000097:blood; D003404:Creatinine / Q000097:blood; D004912:Erythrocytes / Q000032:analysis / Q000201:enzymology / Q000378:metabolism*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D011188:Potassium / Q000097:blood; D012964:Sodium / Q000097:blood / Q000378:metabolism*; D014511:Uremia / Q000097:blood*
D000255:Adenosine Triphosphate; D012964:Sodium; D003404:Creatinine; D005954:Glucosephosphate Dehydrogenase; D000251:Adenosine Triphosphatases; D011188:Potassium