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Phosphodiesterase


Official Full Name
Phosphodiesterase
Background
A phosphodiesterase (PDE) is an enzyme that breaks a phosphodiester bond. Usually, phosphodiesterase refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. However, there are many other families of phosphodiesterases, including phospholipases C and D, autotaxin, sphingomyelin phosphodiesterase, DNases, RNases, and restriction endonucleases (which all break the phosphodiester backbone of DNA or RNA), as well as numerous less-well-characterized small-molecule phosphodiesterases.
Synonyms
PDE; Phosphodiesterase 2A; Phosphodiesterase 4A; Phosphodiesterase 5A; Phosphodiesterase 7A

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CatalogNATE-0527
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CatalogNATE-0530
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Related Reading

Phosphodiesterase (PDEs) has the function of hydrolyzing the second messengers in the cell (cAMP, cyclic adenosine monophosphate or cGMP, cyclic guanosine monophosphate), and degrades the intracellular cAMP or cGMP, thereby ending the biochemical effects conducted by these second messengers. cAMP and cGMP play an important role in regulating cell activities. The adjustment of its concentration is mainly determined by the balance between the synthesis of adenylate cyclase and the hydrolysis of phosphodiesterase (PDEs). PDEs are widely distributed in the human body, and their physiological effects involve many research fields. In recent years, as new therapeutic targets, PDEs have attracted wide attention from many scholars and become a new research hotspot. The clinical research of selective PDE 4 and PDE 5 inhibitors has received special attention.

cGMP Figure 1. cGMP.

Genotyping

Molecular cloning technology reveals that phosphodiesterases (PDEs) are a large multi-gene family. The development of selective phosphodiesterases inhibitors will open up new ideas for the treatment of many diseases. PDEs are a large family of multiple genes. It includes 11 types and more than 30 types of phosphodiesterase isoenzymes with different substrate specificities, enzyme kinetic characteristics, regulatory characteristics, and cell and subcellular distribution areas. Similar structures contain two functional areas: regulation and catalysis. The amino acid sequences of the catalytic regions of all types of PDEs are more than 75% identical. Show the homology between family members. And determines the specificity of the substrate or inhibitor. PDEs have different substrate specificities: PDE 4, 7, and 8 acts exclusively on cAMP, while PDE 5, 6, and 9 acts selectively on cGMP. PDE3 binds to cAMP and cGMP with similar affinity, but relatively does not hydrolyze cGMP, so it is considered functionally specific to cAMP, and cGMP acts as a negative regulator through competitive binding with enzyme sites.

Classifications

Genotyping

Molecular cloning technology reveals that phosphodiesterases(PDEs) are a large multi-gene family. The development of selective phosphodiesterases inhibitors will open up new ideas for the treatment of many diseases. PDEs are a large family of multiple genes. It includes 11 types and more than 30 types of phosphodiesterase isoenzymes with different substrate specificities, enzyme kinetic characteristics, regulatory characteristics, and cell and subcellular distribution areas. Similar structures contain two functional areas: regulation and catalysis. The amino acid sequences of the catalytic regions of all types of PDEs are more than 75% identical. Show the homology between family members. And determines the specificity of the substrate or inhibitor. PDEs have different substrate specificities: PDE 4, 7, and 8 acts exclusively on cAMP, while PDE 5, 6, and 9 acts selectively on cGMP. PDE3 binds to cAMP and cGMP with similar affinity, but relatively does not hydrolyze cGMP, so it is considered functionally specific to cAMP, and cGMP acts as a negative regulator through competitive binding with enzyme sites.

Mechanism

As the second messenger of neurotransmitters, hormones, light and odor, cAMP and cGMP widely act on target organs in cells, such as kinases, ion channels and various PDEs. When external signals are transmitted across the membrane and cause a series of physiological reactions to activate nucleotide cyclase (as shown in Figure 1), cAMP and cGMP are produced. The mission of the PDEs family is to hydrolyze and inactivate them into 5-mono Monophosphate nucleoside5 (AMP). The balance between the synthesis of nucleotide cyclase and the hydrolytic inactivation of PDEs determines the concentration of the second messengers cAMP and cGMP. It is worth noting that cGMP is not only hydrolyzed by PDEs, but also can regulate the activity of some PDEs. For example, PDE2 can be stimulated by cGMP, while PDE3 can be inhibited by cGMP, and PDE4 is not sensitive to cGMP.


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