Driving the Sodium Pump backwards to form Adenosine Triphosphate

Abstract

IF the ionic pump in the red cell membrane expels three sodium ions and takes up about two potassium ions for each molecule of adenosine triphosphate (ATP) hydrolysed^1–5, under physiological conditions the free energy available to drive the reaction forwards must be quite small—about 3,000 cal. By arranging that the concentration gradients for sodium and potassium are even more adverse, it should be thermodynamically possible to run the pump backwards and synthesize ATP, though, of course, theory cannot predict that the reaction would occur at a measurable rate. Investigators who have looked for ATP–inorganic phosphate (P_i) exchange associated with “transport ATPase” activity^6,7 have never found it, but they have always looked in broken cell preparations where ionic concentrations must be the same on both sides of the membrane and where, in consequence, the free energy change for the overall reaction is likely to be heavily in favour of ATP breakdown. An ingenious attempt to reverse the sodium pump in perfused squid axons failed, but it failed in such a way as to leave the possibility of reversal still an open question⁸. More encouraging was the finding that red cells with intact membranes show peculiar behaviour when placed in solutions lacking potassium, and the effect of internal phosphate concentration on this behaviour suggests that the final stage of ATP hydrolysis—Pi release—may be reversible⁹.