USE OF ISOTOPICALLY RADIOLABELED GM3 GANGLIOSIDE TO STUDY METABOLIC ALTERATIONS IN SALLA-DISEASE

We report the preparation of radioactive GM3 ganglioside and its use i n the study of sialic acid storage disorders. For the first time GM3 w as isotopically radiolabeled in three positions of the molecule: at th e sialic acid acetyl group, [H-3-Neu5Ac]GM3, at the C1 of the fatty ac id moiety, [[C-14-Stearoyl]GM3, and at C3 of sphingosine, [H-3-Sph]GM3 . The radioactive GM3 administered to cultured human fibroblasts from a patient suffering from Salla disease was taken up by the cells and m etabolized. An analysis of the distribution of radioactivity within th e ganglioside metabolic derivatives showed an accumulation of free sia lic acid and ceramide in the pathological cells.