RECENT ADVANCES IN THE BIOCHEMISTRY OF SPHINGOLIPIDOSES

Glycosphingolipids are ubiquitous membrane components of eukaryotic ce lls, They participate in various cell recognition events and can regul ate enzymes and receptors within the plasma membrane, Sphingolipidoses are due to an impaired lysosomal digestion of these substances, Glyco sphingolipids are degraded by the action of exohydrolases, which are s upported, in the case of glycosphingolipids with short oligosaccharide chains, by sphingolipid activator proteins, Five sphingolipid activat or proteins are known so far, the GMP-activator and the SAPs, SAP-A to D (also called saposins), Degradation of glycosphingolipids requires endocytic membrane flow of plasma membrane derived glycosphingolipids into the lysosomes, Recent research focused on the topology of this pr ocess and on the mechanism and physiological function of sphingolipid activator proteins, Limited knowledge is available about enzymology an d topology of glycosphingolipid biosynthesis, Recently, intermediates of this metabolic pathway have been identified as novel signalling mol ecules, Inhibition of glycosphingolipid biosynthesis has been shown to be beneficial in the animal model of Tay-Sachs disease, Mice with dis rupted genes for lysosomal hydrolases and activator proteins are usefu l models for known human diseases and are valuable tools for the study of glycosphingolipid metabolism, the pathogenesis of sphingolipidoses and novel therapeutic approaches.