Functionally abnormal Na+-K+ pump in erythrocytes of a morbidly obese patient.
The Na(+)-K(+) pump in the erythrocytes of a mordibly obese patient shows a unique constellation of functional abnormalities. The number of pump units, measured by [(3)H]ouabain binding to intact cells, as well as the enzymatic activity of the (Na(+)-K(+))-dependent ATPase in erythrocyte membranes were found to be markedly increased compared with control cells (18-fold and 14-fold, respectively). There was a concomitant fivefold increase in the rate of pump-mediated uptake of (86)Rubidium (a K analogue); this was balanced by an increased rate of (86)Rb efflux. In striking contrast to normal cells, however, a major portion of this efflux (80%) was inhibited by ouabain, and thus appeared to be mediated by the Na(+)-K(+) pump. Erythrocytes from this patient had elevated levels of intracellular K(+) and reduced levels of intracellular Na(+). This finding, taken together with the ouabain inhibition of K(+) efflux and the absence of associated abnormalities, argues against the possibility that the increased number of Na(+)-K(+) pump units was a compensation for a primary increase in the permeability of the erythrocyte membrane to monovalent cations, as is seen in a variety of erythrocyte disorders. Further evidence for a primary abnormality of the enzyme was our observation that the cardiac glycoside ouabain bound to these cells with reduced affinity and had a right shifted dose response for pump inhibition. The markedly increased number of Na(+)-K(+) pump units in these cells did not appear to extend to mononuclear leukocytes.In conclusion, the erythrocytes from this patient have a very large number of functionally abnormal Na(+)-K(+) ATPase units. A unique abnormality of the erythrocyte Na(+)-K(+) ATPase of these cells is the most likely explanation for these findings.
D001693:Biological Transport, Active; D004910:Erythrocyte Membrane / Q000201:enzymology* / Q000378:metabolism; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology; D009765:Obesity / Q000201:enzymology*; D010042:Ouabain / Q000378:metabolism; D011188:Potassium / Q000097:blood; D011972:Receptor, Insulin / Q000097:blood; D012413:Rubidium / Q000378:metabolism; D012964:Sodium / Q000097:blood; D000254:Sodium-Potassium-Exchanging ATPase / Q000097:blood*
D010042:Ouabain; D012964:Sodium; D011972:Receptor, Insulin; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium; D011188:Potassium