| Modification Notes |
Sphingomyelin (SM) is a lipid that is found in the membranous myelin sheath surrounding nerve cell axons. Sphingomyelin is made up of sphingosine and fatty acids and potentially plays a role in signal transduction. SM hydrolysis is involved in colonic tumorigenesis and cholesterol absorption, and it is also a source of various lipid messengers. It is triggered in a bile salt-dependent manner by intestinal alkaline sphingomyelinase (Alk-SMase), which is expres-sed in the intestinal mucosa and human bile. Alk-SMase is an ectoenzyme related to the NPP (nucleotide phosphodiesterase) family with five potential N-glycosylation sites and integral membrane domains at each termini. Trypsin cleaves Alk-SMase at its C-terminus, thereby releasing it from the mucosa and enhancing its activity. In the colon, Alk-SMase displays anti-proliferative and anti-inflammatory properties by generating ceramide, reducing the formation of lysophosphatidic acid and inactivating platelet-activating factor. Alk-SMase is downregulated in human long-standing ulcerative colitis and colonic adenocarcinoma, and mutations in the Alk-SMase gene may lead to colon cancer. |
