THE BIOCHEMISTRY OF SODIUM TRANSPORT.

Summary 1. The biochemistry of ion transport has been considered in its relationship to the metabolism of phosphate compounds. 2. The supply of energy for active sodium transport has been discussed and it is concluded that the immediate source of this energy is adenosine triphosphate. 3. The stoichiometry of sodium transport in its relation to the energy source has been considered under two headings: the ratio between oxygen consumption and sodium carriage and that between use of ATP and sodium carriage. It appears that the figures for the former are uncertain enough to preclude any conclusions based upon them. Conclusions from the sodium/ATP ratio are also unlikely to be firmly based. It is thus difficult to decide whether the sodium transport system depends upon a direct conversion of ATP energy or whether it depends upon an indirect mechanism. 4. The possible mechanisms for utilization of ATP are considered from various points of view. The demonstration that enzyme systems are capable of ‘hydrolysing’ ATP in the presence of sodium and potassium is discussed. It is pointed out that such systems must conceal several steps which occur between an initial reaction and the We are indebted to Dr Alex Leaf, Massachusetts General Hospital, Dr A. E. M. McLean, Medical Research Council, London, and Dr D. Reichenberg, National Chemical Laboratory, for detailed help with the manuscript and for giving us their views on substantial parts of the work. Dr E. J. Harris, University College London, and Dr K. R. Rees, University College Hospital, Medical School, London, discussed many details with us. We are indebted to Professor E. Baldwin and Dr S. P. Datta, University College London, for making these lectures possible, and to the CIBA Foundation for assistance in making a visit to London for this purpose. The work was undertaken during the tenure of grants from the National Cancer Institute, the Burroughs-Wellcome Fund, the Damon Runyon Fund and Charles Pfizer and Co. The possibility that phosphoproteins may act as sodium carriers is discussed. The evidence is fairly strong that there is a relationship between sodium transport and these molecules, but the nature of the relationship and many important details are obscure. 5. The actions of certain drugs on sodium transport are described. Some of these, which are not usually thought of as inhibitors of active transport but rather as stabilizers, are shown to inhibit potassium uptake and sodium extrusion in nonexcitable tissues such as liver, erythrocytes and ascites tumour cells. Their effect indistinguishable from that of strophanthin-G in that it is reversed by excess potassium, both with regard to whole cells and to the sodium- and potassium-activated ATP-ases. Like strophanthin-G, these drugs inhibit phosphoprotein turnover in appropriate systems. 6. The relationship between sodium and calcium in cells is discussed. I t is pointed out that there is a reciprocal relationship between these, but that calcium transport depends upon sodium transport. Many observations which suggest that a given transport or other function depends upon the concentration of external sodium may in fact result from the influx of calcium. Similarly, the effect of strophanthin-G and of low external potassium may also be mediated by calcium influx or intracellular calcium shifts. A speculation on the nature of the permeability and other changes during the generation of the action potential is included.