Energy metabolism in human erythrocytes. I. Effects of sodium fluoride.
Exposure of red cells to fluoride produces a variety of metabolic alterations, most of which are based upon the secondary effects of enolase inhibition, which reduces pyruvate synthesis and interferes with the regeneration of diphosphopyridine nucleotide (NAD). Adenosine triphosphate (ATP) is consumed in the hexokinase and phosphofructokinase reactions but is not regenerated since the deficiency of NAD limits glyceraldehyde phosphate dehydrogenase. ATP depletion in the presence of fluoride and calcium induces a massive loss of cations and water. Of the other known sites of ATP utilization, membrane-bound ATPase is inhibited by fluoride, but the incorporation of fatty acids into membrane phospholipids is unaffected until ATP is depleted. The addition of methylene blue to fluoride-treated red cells regenerates NAD, permitting triose oxidation and the generation of 3-phosphoglycerate and 2,3-diphosphoglycerate. Enolase inhibition is then partially overcome by mass action, and sufficient glycolysis proceeds to maintain the concentration of ATP. This in turn prevents the massive cation and water loss, and permits membrane phospholipid renewal to proceed. Membrane ATPase activity is not restored by the oxidant so that normal cation leakage remains unopposed by cation pumping in red cells exposed to the combination of fluoride and methylene blue.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000255:Adenosine Triphosphate / Q000378:metabolism; D000745:Anemia, Hemolytic, Congenital / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D046508:Culture Techniques; D004912:Erythrocytes / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005459:Fluorides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D006836:Hydro-Lyases / Q000037:antagonists & inhibitors*; D008751:Methylene Blue / Q000494:pharmacology; D009243:NAD / Q000096:biosynthesis; D010084:Oxidation-Reduction; D010732:Phosphofructokinase-1 / Q000378:metabolism; D010743:Phospholipids / Q000096:biosynthesis; D010751:Phosphopyruvate Hydratase / Q000037:antagonists & inhibitors; D011773:Pyruvates / Q000096:biosynthesis; D012964:Sodium / Q000494:pharmacology; D014882:Water-Electrolyte Balance / Q000187:drug effects
D005227:Fatty Acids; D010743:Phospholipids; D011773:Pyruvates; D009243:NAD; D000255:Adenosine Triphosphate; D012964:Sodium; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D006593:Hexokinase; D010732:Phosphofructokinase-1; D000251:Adenosine Triphosphatases; D006836:Hydro-Lyases; D010751:Phosphopyruvate Hydratase; D005459:Fluorides; D002118:Calcium; D008751:Methylene Blue