Fig. 1.

An integration of pathways and metabolism of biological purines: intracellular ATP is partly metabolized by adenylate cyclase (AC) to cAMP which could activate PKA. Cells release ATP through pannexin channels under stress. The accumulation of extracellular ATP is dephosphorylated to adenosine by 4 ecto-nucleotidases including CD39, CD73, NPPs, and alkaline phosphatases. Adenosine can further be metabolized by adenosine deaminase (ADA) to inosine (I) and hypoxanthine (HypoX) or function as a signaling molecule by activation of its adenosine receptors on multiple cell types. Once uptake by equilibrative nucleoside transporters (ENTs), adenosine is further metabolized by ADA to inosine, S-adenosylhomocytesine hydrolase (SAHH) to adenosylhomocysteine (AdoHcy) or adenosine kinase (ADK) to AMP, which could stimulate AMPK when [AMP]/[ATP] ratio escalates