Intracellular ATP Concentration and Implication for Cellular Evolution

SIMPLE SUMMARY: The lens organ of the eye and muscle tissue exist at opposite ends of the metabolic spectrum. Lens is metabolically quiescent using little energy, while muscle has high energy requirements. However, both tissues contain excessively high millimolar concentrations of adenosine triphosphate (ATP) molecules, the biochemical energy source for all of life’s activities. Nature does not manufacture excess ATP molecules, and thus the question becomes: Why this dichotomy? To answer this question, we prepared a compilation of measured ATP concentrations from cells/tissues/organs across three phylogenetic domains of life: eukaryotes, archaea, and prokaryotes. Among a total of 136 organ/tissue/cell sources, we found that all specimens examined contained excessively high concentrations of ATP (average~4.4 millimolar), regardless of how they lived or their function. Since these specimens only require a small micromolar amount of ATP for energy metabolism, this observation reinforced the notion that ATP has another major function in life. The recent demonstration that ATP acts as a protein solvating agent keeping proteins in their active forms prevents aggregation and in high concentrations may avert a multitude of diseases. The presence of high concentrations of ATP across phylogenetic domains suggests another role for ATP fundamental to cellular/tissue/organ function and biological, biochemical, and biophysical evolution. ABSTRACT: Crystalline lens and striated muscle exist at opposite ends of the metabolic spectrum. Lens is a metabolically quiescent tissue, whereas striated muscle is a mechanically dynamic tissue with high-energy requirements, yet both tissues contain millimolar levels of ATP (>2.3 mM), far exceeding their underlying metabolic needs. We explored intracellular concentrations of ATP across multiple cells, tissues, species, and domains to provide context for interpreting lens/striated muscle data. Our database revealed that high intracellular ATP concentrations are ubiquitous across diverse life forms including species existing from the Precambrian Era, suggesting an ancient highly conserved role for ATP, independent of its widely accepted view as primarily “metabolic currency”. Our findings reinforce suggestions that the primordial function of ATP was non-metabolic in nature, serving instead to prevent protein aggregation.