CO2/HCO3--responsive soluble adenylyl cyclase as a putative metabolic sensor

Cyclic AMP (cAMP) is an evolutionarily conserved regulator of metabolism. Recently, we identified a novel mammalian source of cAMP - soluble adenylyl cyclase (sAC) - that is regulated directly by bicarbonate ions (HCO3-). As the concentration of HCO3- reflects cellular levels of carbon dioxide (CO2), energy-generating metabolic processes (which increase intracellular CO2) are poised to activate bicarbonate-responsive sAC. This direct link between metabolic activity, sAC and cAMP could represent an evolutionarily conserved mechanism of metabolic feedback regulation.