The Metabolism of Tay-Sachs Ganglioside: Catabolic Studies with Lysosomal Enzymes from Normal and Tay-Sachs Brain Tissue

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1972 Sep 1

PMID 4639018

Citations 8

Authors

J F Tallman

W G Johnson

R O Brady

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Activity of hydrolytic enzymes in various regions of normal human brain tissue.

Prabha M, Ravi V, Ramachandra Swamy N Indian J Clin Biochem. 2014; 28(3):283-91.

PMID: 24426225 PMC: 3689325. DOI: 10.1007/s12291-012-0273-0.

Benefits from unearthing "a biochemical Rosetta Stone".

Brady R J Biol Chem. 2010; 285(53):41216-21.

PMID: 21030589 PMC: 3009847. DOI: 10.1074/jbc.X110.197954.

Enzyme replacement therapy: conception, chaos and culmination.

Brady R Philos Trans R Soc Lond B Biol Sci. 2003; 358(1433):915-9.

PMID: 12803925 PMC: 1693186. DOI: 10.1098/rstb.2003.1269.

Cellular localization of neuraminidases in cultured human fibroblasts.

Zeigler M, Bach G Biochem J. 1981; 198(3):505-8.

PMID: 7326018 PMC: 1163295. DOI: 10.1042/bj1980505.

Delivery of hexosaminidase A to the cerebrum after osmotic modification of the blood--brain barrier.

Neuwelt E, Barranger J, Brady R, Pagel M, Furbish F, Quirk J Proc Natl Acad Sci U S A. 1981; 78(9):5838-41.

PMID: 6946518 PMC: 348880. DOI: 10.1073/pnas.78.9.5838.

References

Sandhoff K, Andreae U, JATZKEWITZ H . Deficient hexozaminidase activity in an exceptional case of Tay-Sachs disease with additional storage of kidney globoside in visceral organs. Life Sci. 1968; 7(6):283-8. DOI: 10.1016/0024-3205(68)90024-6. View

Pilz H, Muller D, Sandhoff K, Ter Meulen V . [Tay-Sachs disease with hexosaminidase deficiency. Clinical, morphological and biochemical findings in a case with visceral storage of renal globosides]. Dtsch Med Wochenschr. 1968; 93(39):1833-9 passim. DOI: 10.1055/s-0028-1110836. View

Brady R . The sphingolipidoses. N Engl J Med. 1966; 275(6):312-8. DOI: 10.1056/NEJM196608112750606. View

Robinson D, Stirling J . N-Acetyl-beta-glucosaminidases in human spleen. Biochem J. 1968; 107(3):321-7. PMC: 1198666. DOI: 10.1042/bj1070321. View

FROHWEIN Y, Gatt S . Enzymatic hydrolysis of sphingolipids. VI. Hydrolysis of ceramide glycosides by calf brain beta-N-acetylhexosaminidase. Biochemistry. 1967; 6(9):2783-7. DOI: 10.1021/bi00861a019. View

Suzuki Y, Jacob J, Kutty K, Suzuki K . Gm2-gangliosidosis with total hexosaminidase deficiency. Neurology. 1971; 21(4):313-28. DOI: 10.1212/wnl.21.4.313. View

Svennerholm L . Quantitative estimation of sialic acids. II. A colorimetric resorcinol-hydrochloric acid method. Biochim Biophys Acta. 1957; 24(3):604-11. DOI: 10.1016/0006-3002(57)90254-8. View

Sandhoff K . Variation of beta-N-acetylhexosaminidase-pattern in Tay-Sachs disease. FEBS Lett. 1969; 4(4):351-354. DOI: 10.1016/0014-5793(69)80274-7. View

Bartsch G . Glycolipid abnormalities in a myoclonic variant of late infantile amaurotic idiocy. J Lipid Res. 1970; 11(3):241-7. View

10.

Ho M, OBrien J . Gaucher's disease: deficiency of 'acid' -glucosidase and reconstitution of enzyme activity in vitro. Proc Natl Acad Sci U S A. 1971; 68(11):2810-3. PMC: 389531. DOI: 10.1073/pnas.68.11.2810. View

11.

OBrien J, Okada S, Ho M, Fillerup D, Veath M, Adams K . Ganglioside storage diseases. Fed Proc. 1971; 30(3):956-69. View

12.

Kolodny E, Brady R, Quirk J, Kanfer J . Preparation of radioactive Tay-Sachs ganglioside labeled in the sialic acid moiety. J Lipid Res. 1970; 11(2):144-9. View

13.

Leibovitz Z, Gatt S . Enzymatic hydrolysis of sphingolipids. VII. Hydrolysis of gangliosides by a neuraminidase from calf brain. Biochim Biophys Acta. 1968; 152(1):136-43. DOI: 10.1016/0005-2760(68)90015-5. View

14.

Sellinger O, Nordrum L . A regional study of some osmotic, ionic and age factors affecting the stability of cerebral lysosomes. J Neurochem. 1969; 16(8):1219-29. DOI: 10.1111/j.1471-4159.1969.tb05969.x. View

15.

Kolodny E, Brady R, VOLK B . Demonstration of an alteration of ganglioside metabolism in Tay-Sachs disease. Biochem Biophys Res Commun. 1969; 37(3):526-31. DOI: 10.1016/0006-291x(69)90947-4. View

16.

Tallman Jr J, Brady R, Suzuki K . Enzymic activities associated with membranous cytoplasmic bodies and isolated brain lysosomes. J Neurochem. 1971; 18(9):1775-7. DOI: 10.1111/j.1471-4159.1971.tb03754.x. View

17.

Sandhoff K, Harzer K, Wassle W, JATZKEWITZ H . Enzyme alterations and lipid storage in three variants of Tay-Sachs disease. J Neurochem. 1971; 18(12):2469-89. DOI: 10.1111/j.1471-4159.1971.tb00204.x. View

18.

Svennerholm L . The chemical structure of normal human brain and Tay-Sachs gangliosides. Biochem Biophys Res Commun. 1962; 9:436-41. DOI: 10.1016/0006-291x(62)90030-x. View

19.

Okada S, OBrien J . Tay-Sachs disease: generalized absence of a beta-D-N-acetylhexosaminidase component. Science. 1969; 165(3894):698-700. DOI: 10.1126/science.165.3894.698. View

20.

Kolodny E, KANFER J, Quirk J, Brady R . Properties of a particle-bound enzyme from rat intestine that cleaves sialic acid from Tay-Sachs ganglioside. J Biol Chem. 1971; 246(5):1426-31. View