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Cyclic Nucleotide Metabolism - cAMP. SIGMA-ALDRICH. Cyclic Nucleotide Metabolism - cAMP
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Cyclic Nucleotide Metabolism - cAMP SIGMA-ALDRICH
Cyclic Nucleotide Metabolism - cAMP Cyclic nucleotides have been extensively studied as second messengers of intracellular events initiated by activation of many types of hormone and neurotransmitter receptors. Receptors that stimulate the conversion of ATP to cyclic 3’, 5’-adenosine monophosphate (cAMP) are associated with G proteins. Binding of the hormone or neurotransmitter to its membrane-bound receptor induces a conformational change in the receptor that leads to activation of the -subunit of the G protein. The activated Gs subunit stimulates, while the Gi subunit inhibits adenylyl cyclase (AC). Stimulation of AC catalyzes the conversion of cytoplasmic ATP to cAMP. cAMP activates cAMP-dependent protein kinases, including protein kinase A (PKA). By catalyzing the phosphorylation (activation or deactivation) of intracellular enzymes, cAMP-dependent kinases elicit a wide array of metabolic and functional processes. Negative regulation can occur in the pathway when phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP to adenosine-5’-monophosphate (5’-AMP). Several families of phosphodiesterases (PDE-I-VI) act as regulatory switches by catalyzing the degradation of cAMP to adenosine-5-monophosphate (5’-AMP). PDE II is a low affinity PDE that can cleave both cAMP and cGMP. The activity of PDE II is stimulated by cGMP. PDE III is a low affinity PDE that is inhibited by cGMP and is involved in the regulation of smooth muscle and cardiac contraction. PDE IV is highly selective for cAMP and is the high affinity PDE present in most cell types. References Francis, S.H., and Corbin, J.D., Cyclic nucleotide-dependent protein kinases: intracellular receptors for cAMP and cGMP action. Crit. Rev. Clin. Lab. Sci., 36, 275-328 (1999). Juilfs, D.M., et al., Cyclic GMP as substrate and regulator of cyclic nucleotide phosphodiesterases (PDEs). Rev. Physiol. Biochem. Pharmacol., 135, 67-104 (1999). Simonds, W.F., G protein regulation of adenylate cyclase. Trends Pharmacol. Sci., 20, 66-73 (1999).