ENPP7: The Potential Drug Target and Biomarker for Alkaline Sphingomyelinase

Target Name: ENPP7

NCBI ID: G339221

ENPP7: The Potential Drug Target and Biomarker for Alkaline Sphingomyelinase

Sphingomyelinase (SMase) is a enzyme that is involved in the breaking down of sphingomyelin, a major component of cell membranes. There are four main isoforms of SMase, including SMase A, SMase B, SMase C, and SMase D. Of these, ENPP7 is a potential drug target and biomarker for alkaline sphingomyelinase (ASM) due to its unique structure and function. In this article, we will discuss the properties of ENPP7 and its potential as a drug target and biomarker for ASM.

Structure and Function of ENPP7

ENPP7 is a 23 kDa sphingomyelinase that is expressed in various cell types, including liver, pancreas, and heart. It has a unique catalytic mechanism, where it uses a specific active site to cleave the C-terminus of sphingomyelin. This unique mechanism allows ENPP7 to be specific for its target, which is alkaline sphingomyelinase (ASM).

ASM is a potent enzyme that is involved in the production of reactive oxygen species (ROS) and the oxidation of lipids. ROS can cause damage to cellular membranes, leading to various diseases, including neurodegenerative diseases, cancer, and cardiovascular diseases. ASM also plays a key role in the regulation of cellular signaling pathways, including the production of pro-inflammatory cytokines.

ENPP7's Unique Structure and Function

The unique structure and function of ENPP7 make it an attractive drug target for ASM. ENPP7 has a single catalytic active site that is located at the C-terminus of its substrate, sphingomyelin. This site is important for the specificity of its catalytic mechanism, as it allows ENPP7 to use a specific cleavage mechanism to break down ASM.

The cleavage mechanism of ENPP7 involves a two-step process. First, ENPP7 uses a specific cleavage mechanism to cleave the N-terminus of ASM. This creates a 21 amino acid fragment that is then released from the enzyme. Second, ENPP7 uses a different cleavage mechanism to cleave the C-terminus of ASM, resulting in the formation of a 9 amino acid fragment.

The unique cleavage mechanism of ENPP7 allows it to be specific for ASM, as it does not have the capability to cleave other isoforms of SMase. This specificity is important for the development of effective ASM inhibitors that can be targeted to treat ASM-related diseases.

ENPP7's Potential as a Drug Target

The potential of ENPP7 as a drug target for ASM is due to its unique structure and function. ENPP7's specific cleavage mechanism allows it to be a potent inhibitor of ASM, with potential for ASM inhibition in cell culture models. Additionally, ENPP7 has been shown to be involved in the production of ROS and pro-inflammatory cytokines, which can contribute to the development of ASM-related diseases.

ENPP7 has also been shown to have potential as a biomarker for ASM. The production of ROS and pro-inflammatory cytokines by ENPP7 can be used as a marker for ASM activity. This can be used to monitor the effectiveness of ASM inhibitors and to determine the potential efficacy of new ASM treatments.

Conclusion

ENPP7 is a unique enzyme that has the potential to be a drug target and biomarker for ASM. Its unique structure and function, as well as its involvement in the production of ROS and pro-inflammatory cytokines, make it an attractive target for the development of ASM inhibitors. Further research is needed to fully understand the potential of ENPP7 as a drug

Protein Name: Ectonucleotide Pyrophosphatase/phosphodiesterase 7

Functions: Choline-specific phosphodiesterase that hydrolyzes sphingomyelin releasing the ceramide and phosphocholine and therefore is involved in sphingomyelin digestion, ceramide formation, and fatty acid (FA) absorption in the gastrointestinal tract (PubMed:12885774, PubMed:12671034, PubMed:15205117, PubMed:16255717, PubMed:28292932). Has also phospholipase C activity and can also cleave phosphocholine from palmitoyl lyso-phosphatidylcholine and platelet-activating factor (PAF) leading to its inactivation (PubMed:16255717, PubMed:12885774). Does not have nucleotide pyrophosphatase activity (PubMed:12885774). May promote cholesterol absorption by affecting the levels of sphingomyelin derived from either diet or endogenous sources, in the intestinal lumen (By similarity)

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