LAUSR

Adenosine triphosphate (ATP) is the universal biological energy fuel, or nature's gasoline. The vast quantities of ATP required for sustenance of living processes in cells are synthesized by oxidative phosphorylation and photosynthesis. The chemiosmotic theory of energy coupling was proposed by Mitchell more than 50 years ago but has a contentious history. Part of the accumulated body of experimental evidence supports Mitchell's theory, and part of the evidence conflicts with the theory. Although Mitchell's theory was strongly criticized by several prominent scientists, the controversy was never resolved. Certain theoretical arguments and electrostatic calculations were originally made to justify the central tenet of the chemiosmotic theory of electrogenic proton transfer and violation of electrical neutrality in bulk aqueous phases by creation of a delocalized field. However, these calculations have not been scientifically scrutinized previously. Here it is proved from first principles that the original physical arguments and calculations made in support of steady state electrogenic ion transfer and chemiosmosis violate Gauss's law. Nath's two-ion theory of energy coupling in which the field is local, and ion translocation is dynamically electrogenic but overall electroneutral is shown to satisfactorily resolve the difficulties. Characterization of length scales in mitochondrial systems is shown to impose strong constraints on possible mechanisms of energy transduction. Some biological implications for energy coupling, transduction and ATP synthesis arising as a result of the above analysis are discussed. Examples of several other biological processes where the new theory is useful such as apoptosis, muscle contraction, the joint multisite regulation of oxidative phosphorylation and the Krebs cycle, and hindered protein aggregation arising from ATP's hydrotropic properties are outlined.