Reactome | SMPD1 converts sphingomyelin to ceramide

SMPD1 converts sphingomyelin to ceramide

Stable Identifier

R-HSA-9769742

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

Synonyms

Sphingomyelin phosphodiesterase 1 hydrolyses sphingomyelin to ceramide

ReviewStatus

3/5

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SMPD1 converts sphingomyelin to ceramide

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Sphingomyelin (SPHM), a phospholipid located in the outer leaflet of the plasma membrane, encrypts tissue factor (TF) procoagulant activity on the surface of TF-bearing resting cells (Wang J et al., 2017; 2019; 2023). The enzymatic activity of sphingomyelin phosphodiesterase (SMPD1, also known as acid sphingomyelinase (ASM)), hydrolyzes SPHM, thereby removing its inhibitory effect on TF (Wang J et al., 2017, 2023; reviewed by Ansari et al., 2019). Experimental evidence has shown that treatment with SMPD1 (ASM) inhibitors reduces lipopolysaccharide (LPS)-induced TF procoagulant activity and thrombin generation in wild-type (C57BL/6J) mice (Wang J et al., 2019).

This Reactome event shows SMPD1(ASM)-mediated hydrolysis of SPHM within the TF:SPHM complex forming two products, ceramide and phosphocholine, and releasing "decrypted" TF.

Literature References

PubMed ID	Title	Journal	Year
28758160	Sphingomyelin encrypts tissue factor: ATP-induced activation of A-SMase leads to tissue factor decryption and microvesicle shedding Wang, J, Pendurthi, UR, Rao, LVM	Blood Adv	2017
31262782	Acid sphingomyelinase plays a critical role in LPS- and cytokine-induced tissue factor procoagulant activity Wang, J, Pendurthi, UR, Rao, LVM	Blood	2019