Synthesis of adenosine triphosphate at the expense of downhill cation movements in intact human red cells.

1. When red cells that have been starved for about 6 hr are loaded with inorganic phosphate and incubated in high-sodium potassium-free media, the ouabain-sensitive efflux of potassium from the cells is accompanied by a ouabain-sensitive incorporation of inorganic phosphate into ATP. 2. The magnitude of the incorporation varies roughly linearly with the concentration of sodium in the medium. The ratio (ouabain-sensitive potassium efflux)/(ouabain-sensitive ATP synthesis) is probably not much less than 2 nor much greater than 3. 3. Potassium in the medium inhibits the ouabain-sensitive incorporation of phosphate. The concentration of potassium necessary for half-maximal inhibition is about the same as the concentration at which, under similar conditions, ouabain-sensitive potassium influx and the stimulation of ouabain-sensitive potassium efflux are both half-maximal. 4. These observations suggest that the ouabain-sensitive efflux of potassium from red cells incubated in high-sodium potassium-free media is associated with a reversal of the entire pump cycle. In media containing sufficient potassium to saturate the pump, the efflux appears to involve the reversal of only part of the cycle.