Glycosphingolipids--nature, function, and pharmacological modulation.
The discovery of the glycosphingolipids is generally attributed to Johan L. W. Thudichum, who in 1884 published on the chemical composition of the brain. In his studies he isolated several compounds from ethanolic brain extracts which he coined cerebrosides. He subjected one of these, phrenosin (now known as galactosylceramide), to acid hydrolysis, and this produced three distinct components. One he identified as a fatty acid and another proved to be an isomer of D-glucose, which is now known as D-galactose. The third component, with an "alkaloidal nature", presented "many enigmas" to Thudichum, and therefore he named it sphingosine, after the mythological riddle of the Sphinx. Today, sphingolipids and their glycosidated derivatives are the subjects of intense study aimed at elucidating their role in the structural integrity of the cell membrane, their participation in recognition and signaling events, and in particular their involvement in pathological processes that are at the basis of human disease (for example, sphingolipidoses and diabetes type 2). This Review details some of the recent findings on the biosynthesis, function, and degradation of glycosphingolipids in man, with a focus on the glycosphingolipid glucosylceramide. Special attention is paid to the clinical relevance of compounds directed at interfering with the factors responsible for glycosphingolipid metabolism.
Wennekes
Tom
T
Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, P.O. Box 9502, Leiden, The Netherlands.
van den Berg
Richard J B H N
RJ
Boot
Rolf G
RG
van der Marel
Gijsbert A
GA
Overkleeft
Herman S
HS
Aerts
Johannes M F G
JM
D002462:Cell Membrane; D005699:Galactosylceramides / Q000378:metabolism; D005776:Gaucher Disease / Q000628:therapy; D005962:Glucosylceramidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006028:Glycosphingolipids / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D013107:Sphingolipids / Q000096:biosynthesis / Q000378:metabolism
D005699:Galactosylceramides; D006028:Glycosphingolipids; D013107:Sphingolipids; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase; D005962:Glucosylceramidase