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Sphingomyelinases in the regulation of ceramide formation and function
Author(s) -
Hannun Yusuf A
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.191.1
Subject(s) - ceramide , sphingomyelin , sphingolipid , acid sphingomyelinase , lipid signaling , microbiology and biotechnology , ceramide synthase , sphingomyelin phosphodiesterase , biology , biochemistry , mitochondrion , lysosome , enzyme , chemistry , apoptosis , membrane
Intensive research over the past 2 decades has implicated ceramide, a bioactive sphingolipid, in the regulation of apoptosis, cell growth, cell senescence, and inflammation. Emerging evidence, however, is pointing to significant complexities in the metabolism and structure of ceramide with multiple pathways mediated by more than 2 dozen distinct enzymes of ceramide metabolism regulating the formation of ceramide. Indeed, ceramide itself constitutes a family of closely‐related molecules that are distinguished by specific modifications (e.g. chain length of acyl and sphingoid groups, hydroxylations, specific double bonds). These concepts are well illustrated by studies on acid and neutral sphingomyelinases, two key enzymes in ceramide formation. Neutral sphingomyelinases exist in the inner leaflet of the plasma membrane and mitochondria whereas acid sphingomyelinase resides in the lysosome but is also seen extracellularly and in secretory vesicles. Ongoing results suggest unique functions for each subcellular localization of these enzymes that appear to be mediated through distinct ceramides. Thus, studies of ‘ceramide’ are best approached as enzyme‐ and lipid‐specific pathways of cell regulation.