Stimulation of lysosomal sphingomyelin degradation by sphingolipid activator proteins

Lysosomal breakdown of glycosphingolipids with short hydrophilic carbohydra te headgroups is achieved by the simultaneous action of specific hydrolases and sphingolipid activator proteins (SAPs). Activator proteins are conside red to facilitate the enzyme/substrate interaction between water-soluble en zymes and membrane-bound substrates. Sphingomyelin, containing the small hy drophilic phosphorylcholine moiety, is hydrolysed by acid sphingomyelinase (acid SMase). Recent experimental data on the in vivo and in vitro role of activator proteins in sphingomyelin breakdown by acid SMase are reviewed. T hese data combined with the results using homogenous protein preparations a s well as a liposomal assay system mimicking the physiological conditions s uggest that lysosomal sphingomyelin degradation is not critically dependent on any of the known activator proteins. Moreover, evidence is provided tha t the assumed intramolecular activator domain of acid SMase and especially the presence of negatively charged lipids in the lysosomes are sufficient f or sphingomyelin turnover. (C) 1999 Published by Elsevier Science Ireland L td. All rights reserved.