PDE

Phosphodiesterase (PDE)

Phosphodiesterases (PDEs) are a group of enzymes that play a crucial role in cellular signaling by regulating the levels of cyclic nucleotides, such as cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). These enzymes catalyze the hydrolysis of the phosphodiester bond in these cyclic nucleotides, converting them into their inactive forms, AMP and GMP, respectively.

Classification

PDEs are classified into 11 families, PDE1 to PDE11, based on their sequence homology, substrate specificity, regulatory properties, and tissue distribution. Each family has multiple isoforms, which are encoded by different genes or result from alternative splicing of the same gene.

• PDE1 - Calmodulin-dependent PDEs
• PDE2 - cGMP-stimulated PDEs
• PDE3 - cGMP-inhibited PDEs
• PDE4 - cAMP-specific PDEs
• PDE5 - cGMP-specific PDEs
• PDE6 - Photoreceptor PDEs
• PDE7 - cAMP-specific PDEs
• PDE8 - cAMP-specific PDEs
• PDE9 - cGMP-specific PDEs
• PDE10 - Dual-substrate PDEs
• PDE11 - Dual-substrate PDEs

Function

PDEs regulate the intracellular levels of cAMP and cGMP, which are important secondary messengers in various signaling pathways. By controlling the degradation of these cyclic nucleotides, PDEs influence numerous physiological processes, including cardiac function, smooth muscle relaxation, neuronal signaling, and immune response.

Clinical Significance

PDE inhibitors are a class of drugs that block the action of one or more PDE enzymes, leading to increased levels of cAMP or cGMP. These inhibitors have therapeutic applications in various conditions:

• PDE3 inhibitors - Used in the treatment of congestive heart failure and intermittent claudication.
• PDE4 inhibitors - Used in the treatment of chronic obstructive pulmonary disease (COPD) and psoriasis.
• PDE5 inhibitors - Used in the treatment of erectile dysfunction and pulmonary hypertension.

Related Pages

• Cyclic adenosine monophosphate
• Cyclic guanosine monophosphate
• Enzyme
• Signal transduction
• PDE3 inhibitors
• PDE4 inhibitors
• PDE5 inhibitors