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2013 ; ä (215
): 57-76
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Sphingolipid metabolism and neutral sphingomyelinases
#MMPMID23579449
Airola MV
; Hannun YA
Handb Exp Pharmacol
2013[]; ä (215
): 57-76
PMID23579449
show ga
Sphingolipids are an important class of lipid molecules that play fundamental
roles in our cells and body. Beyond a structural role, it is now clearly
established that sphingolipids serve as bioactive signaling molecules to regulate
diverse processes including inflammatory signaling, cell death, proliferation,
and pain sensing. Sphingolipid metabolites have been implicated in the onset and
progression of various diseases including cancer, lung disease, diabetes, and
lysosomal storage disorders. Here we review sphingolipid metabolism to introduce
basic concepts as well as emerging complexities in sphingolipid function gained
from modern technological advances and detailed cell and animal studies.
Furthermore, we discuss the family of neutral sphingomyelinases (N-SMases), which
generate ceramide through the hydrolysis of sphingomyelin and are key enzymes in
sphingolipid metabolism. Four mammalian N-SMase enzymes have now been identified.
Most prominent is nSMase2 with established roles in bone mineralization, exosome
formation, and cellular stress responses. Function for the other N-SMases has
been more enigmatic and is an area of active investigation. The known properties
and potential role(s) of each enzyme are discussed to help guide future studies.
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