Hormones act through binding to specific cellular receptors. Second messengers are often used to transmit the hormonal message to the target metabolic pathway. cAMP is one such second messenger. Cyclic AMP - dependent signal transduction mechanisms involve three separate proteins: (1) a hormone receptor, (2) adenylate cyclase, and (3) a G protein (see here).

cAMP acts to stimulate the kinase cascade (see Figure 13.18, Figure 16.11) by binding to the cAMP-dependent protein kinase. This activates the enzyme and initiates the serial phosphorylation of phosphorylase b kinase and glycogen phosphorylase b, which leads to phosphorolysis of glycogen to yield glucose-1-phosphate.

Coincident with stimulating glycogen breakdown, cAMP exerts two effects in inhibiting glycogen synthesis: (1) phosphorylation of glycogen synthase, causing its inactivation, and (2) inhibition of phosphoprotein phosphatase (PP-1), whose activity would tend to restore activity of glycogen synthase. PP-1 and other phosphoprotein phosphatases play converse roles in glycogenolysis, in which dephosphorylation of glycogen phosphorylase b kinase (SPK) causes its inactivation.

Effects on Glycolysis/Gluconeogenesis

cAMP ultimately controls the level of fructose-2,6-bisphosphate (the most potent allosteric regulator of glycolysis and gluconeogenesis) through the action of cAMP-dependent protein kinase to interconvert PFK-2 and fructose-2,6-bisphosphatase by phosphorylation.

Reactions involving cAMP

ATP <=> cAMP + PPi (catalyzed by adenylate cyclase)

cAMP + H2O <=> AMP (catalyzed by a phosphodiesterase)