Sphingomyelinase
Sphingomyelinase↓
Blocking synthesis alone leaves this route open. Silencing this enzyme genetically and blocking it with a drug both reproduce the same benefit, so the enzyme is the cause and not a bystander.
In depth
Sphingomyelinase — cuts ceramide straight out of sphingomyelin already sitting in the membrane, bypassing synthesis entirely.
What drives it
Inflammation signal (TNF-α) increases it.
TNF-alpha receptor signaling activates neutral and acid sphingomyelinase to generate ceramide. doi 10.1016/j.redox.2014.07.006
What it drives
It increases Ceramide load.
10.3390/medicina57070729 — Sphingomyelinase hydrolyzes sphingomyelin to ceramide - the second route in, independent of de novo synthesis. The isoforms are compartment-specific and must not be conflated: SMPD1 is acid and lysosomal, SMPD2 is neutral, and a secretory form acts at the outer leaflet of the plasma membrane. Dietary inulin lowered circulating ceramides in mice by suppressing neutral sphingomyelinase specifically - Smpd3 expression fell about two-fold and hepatic neutral SMase activity about three-fold. Shown in mice. No human equivalent has been retrieved. doi 10.3390/medicina57070729
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.