Frontiers in Molecular Biosciences (Nov 2021)
The Proton in Biochemistry: Impacts on Bioenergetics, Biophysical Chemistry, and Bioorganic Chemistry
Abstract
The proton is the smallest atomic particle, and in aqueous solution it is the smallest hydrated ion, having only two waters in its first hydration shell. In this article we survey key aspects of the proton in chemistry and biochemistry, starting with the definitions of pH and pKa and their application inside biological cells. This includes an exploration of pH in nanoscale spaces, distinguishing between bulk and interfacial phases. We survey the Eigen and Zundel models of the structure of the hydrated proton, and how these can be used to explain: a) the behavior of protons at the water-hydrophobic interface, and b) the extraordinarily high mobility of protons in bulk water via Grotthuss hopping, and inside proteins via proton wires. Lastly, we survey key aspects of the effect of proton concentration and proton transfer on biochemical reactions including ligand binding and enzyme catalysis, as well as pH effects on biochemical thermodynamics, including the Chemiosmotic Theory. We find, for example, that the spontaneity of ATP hydrolysis at pH ≥ 7 is not due to any inherent property of ATP (or ADP or phosphate), but rather to the low concentration of H+. Additionally, we show that acidification due to fermentation does not derive from the organic acid waste products, but rather from the proton produced by ATP hydrolysis.
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