C20-sphingosine as a determining factor in aggregation of gangliosides.

Abstract

Aggregation properties of gangliosides, the major synaptic membrane glycosphingolipids of mammalian brain, may prevent their segregation during membrane assembly and promote a uniform membrane matrix with minimum maintenance energy. The sphingosine residues of bovine brain gangliosides show an increase in C20-sphingosine corresponding with an increase in sialic acid. Concentrations of C20-sphingosine varied from 37% for the monosialoganglioside to 64% for the trisialoganglioside, the remainder being C18-sphingosine. Ultracentrifugal analysis showed that changes in sialic acid content and in C20-sphingosine content individually affect micellar size. Increases in sialic acid content decreased micellar size from 225 for the monosialoganglioside to 120 monomersper micelle for the trisialoganglioside. Monosialogangliosides enzymatically prepared from oligosialohomologues with a higher C20-sphingosine content gave evidence for a considerable effect of C20sphingosine upon the free energy of the aggregate form; the number of monomers per micelle increased from 225 for the natural monosialoganglioside to 280 for monosialoganglioside derived from trisialoganglioside. The similar aggregation energies of the major synaptic membrane gangliosides apparently result from a metabolic balancing of increased C20-sphingosine with increased sialic acid content.