Ganglioside Turnover and Formation of Metabolic Regulators

Gangliosides are components of the plasma membrane and their metabolism consists in : de novo biosynthesis, occurring mostly in the Golgi apparatus; catabolism, taking place in the lysosomes; salvage processes (re-cycling of catabolites) with the coordinate participation of lysosomes, endoplasmic reticulum and Golgi apparatus; glycosylation of internalized gangliosides, taking place in the Golgi apparatus. The various steps of ganglioside metabolism are intimately connected with the rapid events of membrane turnover, and occur rapidly themselves. Gangliosides do undergo endocytosis and move from the early endosome compartment partly to the Golgi apparatus, partly to late endosomes and lysosomes. Direct return of gangliosides to the plasma membrane via retro-endocytosis or transport, mediated by carrier proteins, has not yet been explored. Intralysosomal biodegradation of gangliosides leads to formation of sphingosine and ceramide, substances that behave as powerful metabolic regulators. The process appears to be influenced by agents that modify the functional state of the cell. The hypothesis is released that factors capable to affect ganglioside endocytosis do affect the rate of ganglioside metabolic processing, thus changing the concentration of second messengers of sphingoid nature.