Enzymatic remodeling of fatty acid molecules by SCDase demonstrated that fucosyl GM1a possessing a polyunsaturated fatty acid induces apoptosis in HL60 human promyelocyte leukemia cells

Glycosphingolipids show heterogeneity in carbohydrate as well as lipid (ceramide) moieties. However, the biological relevance of the heterogeneity of ceramide has yet to be elucidated. To assess the significance of fatty acid molecules of glycosphingolipids, enzymatic remodeling of fatty acyl chains of glycosphingolipids was performed using sphingolipid ceramide N-deacylase which catalyzes a reversible reaction in which the N-acyl linkage of ceramide is cleaved or synthesized. Using the hydrolysis and condensation reactions of the enzyme, fucosyl GM1a having a single but different fatty acid molecule were synthesized. We found that fucosyl GM1a having polyunsaturated fatty acids (PUFA-Fuc-GM1a) inhibited the proliferation of human leukemia-derived HL60 cells, whereas parental fucosyl GM1a did not. PUFA-Fuc-GM1a, but not lyso-Fuc-GM1a which lacks fatty acid molecules, was found to induce apoptosis in HL60 cells. This study clearly shows that the fatty acid moiety of glycosphingolipids could significantly affect their pharmacological activities.