SMase, acid

The lysosomal hydrolysis of SM to Cer and phosphocholine is catalyzed by acid SMase, a water-soluble, lysosomal glycoprotein that interacts with a sphingolipid-activator protein (SAP) and anionic lipids such as bis(monoacylglycerol)phosphate (BMP) to hydrolyze interfacial SM (T. Linke, 2001). Acid SMase possesses an N-terminal SAP-homology domain that appears to stabilize the correctly folded form of acid SMase as well as to facilitate the interfacial interaction with substrate in vivo (M. Kolzer, 2004). Acidic SMase is also secreted by many types of cells (I. Tabas, 1999 I. Takahashi, 2005). 

Acid SMase-deficient mice have been generated (K. Horinouchi, 1995) and have been useful both as models for Niemann-Pick disease and to study the roles of acid SMase in cell signaling (P. Santana, 1996 D.J. Sillience, 2001). Cer derived from aberrantly high acid SMase activity also appears to play a role in disease because activation of acid SMase and generation of Cer has been found to play a key role in the liver cirrhosis and anemia in Wilson disease, which is caused by accumulation of Cu(2+) in cells (P.A. Lang, 2007). 

All of the above SMases are C type SMases that produce Cer and choline phosphate an SMase D (which produces Cer 1-phosphate and choline) is found in the venom of brown recluse spider, Corynebacterium pseudotuberculosis (which commonly infects sheep). Vibrio damsela (an aquatic bacterium that causes wound infections in humans), and the human pathogen Arcanobacterium haemolyticum. The venom SMase D produces much of the tissue damage caused by these organisms (A.P Truett, 1993) by sustained activation of inflammation (S.H. Farsky, 2005). Interestingly, SMase also acts as a lysophosphatidylcholine phosphodiesterase to produce lysophosphatidic acid, another inflammatory mediator (L.A. van Meeteren, 2004). 

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