Ceramide first step
Serine palmitoyltransferase (SPT)
Also searched as Serine palmitoyltransferase (SPT).
You want it restrained, not abolished. Halving it in mice lowered plasma ceramide by 39-45% with no lipid disturbance; deleting it entirely is embryonic-lethal, strips membrane sphingomyelin and causes liver damage. Partial, pharmacological restraint only.
In depth
Serine palmitoyltransferase — the first and rate-limiting step of building ceramide from scratch, condensing serine with palmitate.
What drives it
Stops fat storage increases it.
Ceramide-metabolism review 2016, Am J Physiol Endocrinol Metab - palmitate, the product of de novo lipogenesis via fatty-acid synthase, is the substrate serine palmitoyltransferase condenses with serine. Lipid oversupply therefore feeds ceramide synthesis at its first committed step, which is the mechanical link between eating pattern and this pathway. Sources:. PMID 28280233
What it drives
It increases Ceramide load.
Serine palmitoyltransferase condenses serine with palmitoyl-CoA - the first and rate-limiting step of de novo ceramide synthesis (Wang 2017, Circulation 135:2028, PMID 28280233; unsaturated fatty acids oppose the saturated-fat drive on this step). Warning carried deliberately: SPT is not a viable therapeutic target. Inhibiting it in rodents lowers ceramide but does so by extreme diminution of all sphingolipids, including the structural ones the body requires. The selective target in this pathway is ceramide synthase, not SPT. PMID 28280233
It increases Ceramide synthase.
Serine palmitoyltransferase generates the sphinganine backbone that ceramide synthase subsequently N-acylates. (Study on file: 10.1016/S1388-1981(02)00335-9 · PMC12132366 · PMC6779703). doi 10.1016/S1388-1981(02 · PMC12132366
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.