The glycosphingolipids of human plasma lipoproteins.

Human plasma contains low concentrations of four neutral glycosphingolipids (glucosylceramide, lactosylceramide, globotriaosylceramide, and globotetraosylceramide) and GM3 ganglioside which occur as part of the plasma lipoproteins, particularly low density lipoprotein (LDL, d 1.006-1.063 g. mL-1) and to a lesser extent with high density lipoprotein (HDL, d 1.063-1.21 g.mL-1). Plasma glucosylceramide appears to exchange freely between plasma lipoproteins and erythrocytes, and probably also between different lipoprotein fractions, in the circulation. Free exchange of other major neutral glycosphingolipids (GSLs) between lipoproteins and erythrocytes, or between lipoprotein fractions, does not normally occur. The GSL profile of each lipoprotein fraction is the same as the overall GSL composition of unfractionated plasma. In Fabry disease and Gaucher disease, GSL storage diseases, the excess glycolipid in plasma is distributed among the various lipoprotein fractions in the same relative proportions as in healthy individuals. In familial hypercholesterolemia, in which the levels of all plasma GSLs are elevated, the excess GSL is largely associated with the increased concentrations of LDL. In patients with hereditary hypolipoproteinemias, the levels of GSL in plasma are decreased less than those of other lipids. The relative excess of GSL in these patients is distributed among the remaining lipoprotein fractions. Excess GSL such as occurs in Fabry disease, does not appear to have a biologically significant effect on the physical stability of human LDL.