American scientists from the University of Pennsylvania have figured out how our bodies recover from stressful situations. The work sheds light on the molecular processes behind the “hit or run” response. The study is published in the Journal of the American Chemical Society (JASC).

Experts focused on protein kinase A (PKA), a key protein that regulates hundreds of processes in the body (from metabolism to memory formation). When stressed or starved, hormones like adrenaline and glucagon set off a chain reaction that activates PKA through the molecule cAMP.

Using advanced imaging techniques, including cryo-electron microscopy, the scientists discovered three previously unknown conformations of the PKA protein complex during the “resetting” process. This discovery can be compared to the discovery of new details in a complex mechanism.

 Phosphodiesterases (PDEs), proteins that remove cAMP and return the system to its original state, play a special role in this process. As the researchers found, with each cycle of activation and resetting, the system becomes more efficient, similar to the way an athlete trains.

The study has important implications for understanding the action of caffeine (a PDE inhibitor), drug effects against obesity, the development of stress-related diseases and processes, and memory formation.