Implication of sphingomyelin/ceramide molar ratio on the biological activity of sphingomyelinase.
Sphingolipid signaling plays an important, yet not fully understood, role in diverse aspects of cellular life. Sphingomyelinase is a major enzyme in these signaling pathways, catalyzing hydrolysis of sphingomyelin to ceramide and phosphocholine. To address the related membrane dynamical structural changes and their feedback to enzyme activity, we have studied the effect of enzymatically generated ceramide in situ on the properties of a well-defined lipid model system. We found a gel-phase formation that was about four times faster than ceramide generation due to ceramide-sphingomyelin pairing. The gel-phase formation slowed down when the ceramide molar ratios exceeded those of sphingomyelin and stopped just at the solubility limit of ceramide, due to unfavorable pairwise interactions of ceramide with itself and with monounsaturated phosphatidylcholine. A remarkable correlation to in vitro experiments suggests a regulation of sphingomyelinase activity based on the sphingomyelin/ceramide molar ratio.
Boulgaropoulos
Beate
B
Institute of Biophysics and Nanosystems Research, Austrian Academy of Sciences, Graz, Austria.
Amenitsch
Heinz
H
Laggner
Peter
P
Pabst
Georg
G
D001409:Bacillus cereus / Q000201:enzymology*; D002462:Cell Membrane / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism*; D006868:Hydrolysis; D010713:Phosphatidylcholines / Q000378:metabolism; D053838:Scattering, Small Angle; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*; D013109:Sphingomyelins / Q000378:metabolism*; D014961:X-Ray Diffraction
D002518:Ceramides; D010713:Phosphatidylcholines; D013109:Sphingomyelins; D013108:Sphingomyelin Phosphodiesterase; C028694:1-palmitoyl-2-oleoylphosphatidylcholine