Cyclic Nucleotide Metabolism - cAMP

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Cyclic Nucleotide Metabolism - cAMP
SIGMA-ALDRICH
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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).