title: The role of oxidized nicotinamide adenine dinucleotide in fluoride inhibition of active sodium transport in human erythrocytes.
abstract: The rate coefficient for (22)Na release from previously labeled human erythrocytes was determined in the presence of 0.1-10 mM sodium fluoride (F). The oxidized nicotinamide adenine dinucleotide (NAD(+)) level at the end of 2 hr of incubation in tris(hydroxymethyl)aminomethane (Tris)-Ringer medium was also measured. Both parameters decreased proportionately as F concentration was raised. Both F-induced changes were immediate and were reversed by 10 mM pyruvate. The decrease in NAD(+) concentration following enolase inhibition by F is attributed to a diminished rate of formation in the reaction catalyzed by lactic dehydrogenase (LDH) with undiminished continued utilization in the reaction catalyzed by glyceraldehyde-3-phosphate dehydrogenase (GAPDH). It is postulated that the NAD(+) lowering limited the GAPDH step, resulting in proportionate decreases in the rates of phosphoglycerate kinase (PGK) and Na,K-dependent adenosine triphosphatase (Na,K-ATPase), a reaction sequence thought to link glycolysis with active Na extrusion. Adding pyruvate with F increased NAD(+) production at the LDH step, thus reactivating GAPDH, PGK, and Na,K-ATPase and leading to the observed restoration of (22)Na release. The results suggest, therefore, that F inhibits active Na transport in intact human erythrocytes indirectly through a lowering of NAD(+), although, direct inhibition of the Na,K-ATPase by F may possibly occur simultaneously.
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000328:Adult; D001693:Biological Transport, Active; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D005459:Fluorides / Q000494:pharmacology*; D006019:Glycolysis; D006801:Humans; D008297:Male; D009243:NAD / Q000032:analysis*; D010042:Ouabain / Q000494:pharmacology; D010751:Phosphopyruvate Hydratase / Q000037:antagonists & inhibitors; D011773:Pyruvates / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D012975:Sodium Isotopes; D013997:Time Factors
chemical_list: D011773:Pyruvates; D012975:Sodium Isotopes; D009243:NAD; D010042:Ouabain; D012964:Sodium; D000251:Adenosine Triphosphatases; D010751:Phosphopyruvate Hydratase; D005459:Fluorides