The metabolism of Tay-Sachs ganglioside: catabolic studies with lysosomal enzymes from normal and Tay-Sachs brain tissue.
The catabolism of Tay-Sachs ganglioside, N-acetylgalactosaminyl- (N-acetylneuraminosyl) -galactosylglucosylceramide, has been studied in lysosomal preparations from normal human brain and brain obtained at biopsy from Tay-Sachs patients. Utilizing Tay-Sachs ganglioside labeled with (14)C in the N-acetylgalactosaminyl portion or (3)H in the N-acetylneuraminosyl portion, the catabolism of Tay-Sachs ganglioside may be initiated by either the removal of the molecule of N-acetylgalactosamine or N-acetylneuraminic acid. The activity of the N-acetylgalactosamine-cleaving enzyme (hexosaminidase) is drastically diminished in such preparations from Tay-Sachs brain whereas the activity of the N-acetylneuraminic acid-cleaving enzyme (neuraminidase) is at a normal level. Total hexosaminidase activity as measured with an artificial fluorogenic substrate is increased in tissues obtained from patients with the B variant form of Tay-Sachs disease and it is virtually absent in the O-variant patients. The addition of purified neuraminidase and various purified hexosaminidases exerted only a minimal synergistic effect on the hydrolysis of Tay-Sachs ganglioside in the lysosomal preparations from the control or patient with the O variant of Tay-Sachs disease.
D000328:Adult; D001921:Brain / Q000201:enzymology*; D002247:Carbon Isotopes; D002675:Child, Preschool; D002855:Chromatography, Thin Layer; D046508:Culture Techniques; D005688:Galactosamine; D005732:Gangliosides / Q000378:metabolism*; D006596:Hexosaminidases / Q000302:isolation & purification / Q000378:metabolism* / Q000652:urine; D006801:Humans; D007223:Infant; D008064:Lipidoses / Q000201:enzymology / Q000378:metabolism*; D008247:Lysosomes / Q000201:enzymology*; D009438:Neuraminic Acids; D009439:Neuraminidase / Q000302:isolation & purification / Q000378:metabolism; D014316:Tritium
D002247:Carbon Isotopes; D005732:Gangliosides; D009438:Neuraminic Acids; D014316:Tritium; D005688:Galactosamine; D006596:Hexosaminidases; D009439:Neuraminidase