The degradation of
blood group glycolipid A-6-2 (GalNAc(alpha1-->3)[Fuc alpha1-->2]Gal(beta1-->4)GlcNAc(beta1-->3)Gal(beta1-->4)Glc(beta1-->1')C er, IV2-alpha-fucosyl-IV3-alpha-N-acetylgalactosaminylneolact otetraosylceramide),
tritium-labeled in its
ceramide moiety, was studied in situ, in skin fibroblast cultures from normal controls, from patients with defects of lysosomal
alpha-N-acetylgalactosaminidase, and from patients with other
lysosomal storage diseases. Uptake of the
glycolipid with
apolipoprotein E-coated
liposomes was linear with time and with the amount of
glycolipid added. In normal cells, the expected array of less polar products and some
lipids resulting from re-using the liberated
sphingosine, mainly
sphingomyelin and
phosphatidylcholine, were formed. In
alpha-N-acetylgalactosaminidase-deficient cells, the
glycolipid was virtually not degraded; product formation was less than 2% of the normal control rate, suggesting that
blood group A-active
glycolipids contribute as storage compounds to the pathogenesis of this disease. The expected accumulation of degradation intermediates was seen in
fucosidosis, and in Sandhoff, Gaucher, and
Farber disease cells, whereas normal turnover rates were found in
Tay-Sachs disease cells, G(M2) activator-deficient (variant AB of G(M2)
gangliosidosis) and in
sulfatide activator- (sap-B-) deficient cells. In
G(M1) gangliosidosis and in sap precursor-deficient cells, the lysosomal
glycolipid catabolism was found to be strongly retarded; accumulation of individual products could not be seen. Skin fibroblasts from patients with
alpha-N-acetylgalactosaminidase deficiency (
Schindler disease) cannot degrade the major
blood group A
glycolipid.