Sphingomyelinases: enzymology and membrane activity.
This paper reviews our present knowledge of sphingomyelinases as enzymes, and as enzymes acting on a membrane constituent lipid, sphingomyelin. Six types of sphingomyelinases are considered, namely acidic, secretory, Mg(2+)-dependent neutral, Mg(2+)-independent neutral, alkaline, and bacterial enzymes with both phospholipase C and sphingomyelinase activity. Sphingomyelinase assay methods and specific inhibitors are reviewed. Kinetic and mechanistic studies are summarized, a kinetic model and a general-base catalytic mechanism are proposed. Sphingomyelinase-membrane interactions are considered from the point of view of the influence of lipids on the enzyme activity. Moreover, effects of sphingomyelinase activity on membrane architecture (increased membrane permeability, membrane aggregation and fusion) are described. Finally, a number of open questions on the above topics are enunciated.
Goñi
Félix M
FM
Unidad de Biofísica (CSIC-UPV/EHU), and Departamento de Bioquímica, Universidad del País Vasco, Aptdo. 644, 48080, Bilbao, Spain. gbpgourf@lg.ehu.es
Alonso
Alicia
A
D000818:Animals; D002384:Catalysis; D002462:Cell Membrane / Q000201:enzymology* / Q000378:metabolism; D003001:Cloning, Molecular; D004791:Enzyme Inhibitors; D006801:Humans; D007700:Kinetics; D008051:Lipid Bilayers; D008274:Magnesium / Q000378:metabolism; D008956:Models, Chemical; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013108:Sphingomyelin Phosphodiesterase / Q000737:chemistry* / Q000378:metabolism; D013379:Substrate Specificity; D010738:Type C Phospholipases / Q000378:metabolism
D004791:Enzyme Inhibitors; D008051:Lipid Bilayers; D010738:Type C Phospholipases; C112980:acid sphingomyelinase-1; C112981:acid sphingomyelinase-2; D013108:Sphingomyelin Phosphodiesterase; D008274:Magnesium