Ceramide/sphingosine/sphingosine 1-phosphate metabolism on the cell surface and in the extracellular space.
Sphingolipid metabolites, ceramide, sphingosine, and sphingosine 1-phosphate, have emerged as a new class of lipid biomodulators of various cell functions. These metabolites are known to function not only as intracellular second messengers, but also in the extracellular space. Sphingosine 1-phosphate especially has numerous functions as an important extracellular mediator that binds to cell surface S1P receptors. Recent studies have also shown that sphingolipid-metabolizing enzymes function not only in intracellular organelles but also in the extracellular spaces, including the outer leaflet of the plasma membrane. This review focuses on the metabolic enzymes (acid and alkaline sphingomyelinases, neutral ceramidase, and sphingosine kinase) that are involved in the production of the sphingolipid metabolites in these extracellular spaces, and on the metabolic pathway itself.
Tani
Motohiro
M
Department of Biomembrane and Biofunctional Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12-Nishi 6, Kita-ku, Sapporo 060-0812, Japan.
Ito
Makoto
M
Igarashi
Yasuyuki
Y
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D055572:Ceramidases; D002518:Ceramides / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism; D008246:Lysophospholipids / Q000096:biosynthesis / Q000378:metabolism*; D008954:Models, Biological; D015394:Molecular Structure; D055576:Neutral Ceramidase; D013107:Sphingolipids / Q000096:biosynthesis; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism*
D002518:Ceramides; D008246:Lysophospholipids; D013107:Sphingolipids; C060506:sphingosine 1-phosphate; D013108:Sphingomyelin Phosphodiesterase; D000581:Amidohydrolases; C526744:ASAH2 protein, human; D055572:Ceramidases; D055576:Neutral Ceramidase; D013110:Sphingosine