Energy metabolism in human erythrocytes. . Effect of sodium fluoride

duces a variety of metabolic alterations, most of which are based upon the secondary effects of enolase inhibi-tion, 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 deple-tion in the presence of fluoride and calcium induces a massive loss of cations and water. Of the other known sites of ATP utilization, mem-brane-bound ATPase is inhibited by fluoride, but the incorporation of fatty acids into membrane phospho-lipids 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-di-phosphoglycerate. Enolase inhibition is then partially overcome by mass action, and sufficient glycolysis pro-ceeds 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 oxi-dant so that normal cation leakage remains unopposed by cation pumping in red cells exposed to the combina-tion of fluoride and methylene blue