Evolution and physiological roles of phosphagen systems

Area of Science:

• Biochemistry
• Evolutionary Biology
• Cell Physiology

Background:

• Phosphagens are high-energy phosphate compounds crucial for cellular energy homeostasis.
• They participate in reversible reactions catalyzed by phosphagen kinases, linking energy state to ATP hydrolysis.
• Eight distinct phosphagen systems exist across the animal kingdom, with the creatine phosphate/creatine kinase (CP/CK) system being the most studied.

Purpose of the Study:

• To review the distribution and tissue-specific expression of phosphagen systems within an evolutionary and functional framework.
• To elucidate the roles of phosphagens in cellular energy buffering, inorganic phosphate regulation, and intracellular energy transport.
• To explore the evolutionary origins and functional adaptations of phosphagen systems, particularly the CP/CK system.

Main Methods:

• Literature review and synthesis of existing research on phosphagens and phosphagen kinases.
• Comparative analysis of phosphagen distribution across different animal taxa.
• Evaluation of the functional implications of phosphagen system properties, including thermodynamic poise and diffusivity.

Main Results:

• Phosphagen kinase reactions are vital for temporal ATP buffering, inorganic phosphate (Pi) regulation, and intracellular energy transport.
• The regulation of intracellular Pi levels by phosphagens likely evolved early in evolutionary history.
• The thermodynamic poise of phosphagen kinase reactions significantly influences their regulatory capacity.

Conclusions:

• The evolutionary trajectory of phosphagens highlights their fundamental roles in cellular energy metabolism and adaptation.
• Intracellular targeting of creatine kinase (CK) may have evolved early for efficient energy transport in polarized cells.
• Phosphagens play dynamic roles in metabolic regulation, especially in cells with high and variable energy demands.