The High Millimolar Concentration of ATP: A Fundamental & Foundational Feature of Eukaryotic, Archaeotic, and...

Measurement of the adenosine triphosphate (ATP) concentration among different cells, tissues and organs and even across the phylogenetic tree ordinarily yields exceedingly high concentrations at the millimolar (mM) level. This represents a conundrum in that ATP-driven cellular functions only require micromolar (μM) values. Considering that nature is ordinarily conservative in the generation of high-energy phosphatic metabolites such as ATP, a potential major role for ATP has been completely overlooked and may be of paramount importance because ATP is a hydrotrope. In all phylogenetic domains, reports have established that the excessively high mM concentration of ATP is present in studies of eukaryotic cellular and tissue homogenates, living tissues, and a living organ as well as archaeotic and prokaryotic organisms. These ATP concentrations are also present in contemporary relatives of microorganisms having progenitors existing in the Precambrian Era. This feature is fundamental to cell biology across taxonomic domains. These features are interpreted as serving a foundational molecular function for maintaining organismal homeostasis. We hypothesize that ATP prevents pathological protein aggregation and maintains protein solubility through its hydrotropic feature in cells, tissues, and organs.