Sphingomyelin synthase (SMS)

Sphingomyelin synthase is an enzyme that catalyzes the synthesis of sphingomyelin by transferring a phosphocholine moiety from phosphatidylcholine to ceramide, simultaneously producing diacylglycerol. The mammalian SMS family comprises three members: SMS1, SMS2, and SMSr. SMS1 localizes primarily to the Golgi apparatus, while SMS2 is found at both the Golgi and plasma membrane through S-palmitoylation. SMSr possesses ceramide phosphoethanolamine synthase activity rather than sphingomyelin synthase activity. The enzyme contains a catalytic pentad (E-H/D-H-D) positioned at the interface between lipophilic and hydrophilic segments of its reaction chamber. SMS operates through a two-step synthesis process involving phospholipase C hydrolysis followed by phosphoethanolamine transfer to ceramide. The enzyme sits at the crossroads of sphingomyelin, ceramide, and diacylglycerol metabolism, regulating lipid messengers critical for cell survival, apoptosis, membrane properties, and receptor signaling. SMS modulates protein kinase D recruitment to the Golgi through diacylglycerol production, thereby influencing protein trafficking and cellular secretion pathways.

Other names

SM synthasephosphatidylcholine:ceramide cholinephosphotransferaseceramide:phosphatidylcholine cholinephosphotransferaseSMS1SMS2SMSr (SMS-related)

SMS inhibitors target the catalytic activity of the enzyme to reduce sphingomyelin synthesis, potentially modulating ceramide and diacylglycerol levels for therapeutic benefit in metabolic diseases and cancer.