Abstract
The lysosomal storage diseases are inherited metabolic disorders characterized by the partial or total loss of the activity of specific lysosomal enzymes. This results in the irreversible accumulation of metabolites in lysosomes, ultimately leading to cell death. Many of these disorders are fatal, but less severe forms impair growth and development, often with neurological damage. The prototype lysosomal storage disease is Tay-Sachs disease, resulting from a defect involving β-hexosaminidase (N-acetylhexosaminidase, EC 3.2.1.52).
Supported by the Medical Research Council of Canada Grant PG-4
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References
W. Tay, Symmetrical changes in the region of the yellow spot in each eye of an infant, Trans. Ophthalmol. Soc. U.K. 1:155–155 (1881).
B. Sachs, On arrested cerebral development with special reference to its cortical pathology, J. Nervous Mental Disease. 21:475–475 (1890).
D. Robinson, and J. L. Stirling, N-acetyl-β-glucosaminidases in human spleen, Biochem. L 107:321-327 (1968).
S. Okada, and J. S. O’Brien, Tay-Sachs disease: generalized absence of a β-D-N-acetylhexosaminidase component, Science. 165:698–700 (1969).
D. Mahuran, A. Novak, and J. A. Lowden, The lysosomal hexosaminidase isozymes, Isozymes. Curr. Top. Biol. Med. Res. 12:229–288 (1985).
S. K. Srivastava, and E. Beutler, Hexosaminidase A and hexosaminidase B: studies in Tay-Sachs and Sandhoffs disease, Nature. 241:463–463 (1973).
R. Myerowitz, and N. D. Hogikyan, Different mutations in Ashkenazi Jewish and nonjewish French Canadians with Tay-Sachs disease, Science. 232:1646-1648 (1986).
H. Pilz, D. Moller, K. Sandhoff, and V. Meulen, Tay-Sachische Krankheit mit hexosaminadase defekt, Dtscg. Med. Wochenschr.:93-1833 (1968).
B. F. O’Dowd, M. H. Klavins, H. F. Willard, R. Gravel, J. A. Lowden, and D. J. Mahuran, Molecular heterogeneity in the infantile and juvenile forms of Sandhoff disease (O-variant GM2 Gangliosidosis), J. Biol. Chem. 261:12680-12685 (1986).
E. Conzelmann, and K. Sandhoff, AB variant of infantile GM2 gangliosidosis: deficiency of a factor necessary for stimulation of hexosaminidase A-catalyzed degradation of ganglioside GM2 and glycolipid GA2, Proc. Natl. Acad. Sci. (U.S.A). 75:3979-3983 (1978).
K. Von Figura, and A. Hasilik, Lysosomal enzymes and their receptors, Annual Review of Biochemistry. 55:167-193 (1986).
M. L. Reitman, A. Varki, and S. Kornfeld, Fibroblasts from patients with I-cell disease and pseudo-Hurler poly dystrophy are deficient in uridine 5’-diphosphate-N-acetylglucosamine: glyoprotein N-acetylglucosaminylphosphotransferase activity, J. Clin. InvssL 67:1574-1579 (1981).
R. G. Korneluk, D. J. Mahuran, K. Neote, M. H. Klavins, B. F. O’Dowd, M. Tropak, H. F. Willard, M.-J. Anderson, J. A. Lowden, and R. A. Gravel, Isolation of cDNA clones coding for the a subunit of human β-hexosaminidase: Extensive homology between the a and β subunits and studies on Tay-Sachs disease, J. Biol. Chem. 261:8407-8413 (1986).
B. O’Dowd, F. Quan, H. Willard, A.-M. Lamhonwah, R. Korneluk, J. A. Lowden, R. A. Gravel, and D. Mahuran, Isolation of c-DNA clones coding for the β-subunit of human β-hexosaminidase, Proc. Natl. Acad. Sci. (U.S.A.). 82:1184-1188 (1985).
R. Myerowitz, R. Piekarz, E. F. Neufeld, T. B. Shows, and K. Suzuki, Human β-hexosaminidase a chain: coding sequence and homology with the β chain, Proc. Natl. Acad. Sci. (U.S.A.). 82:7830-7834 (1985).
B. Geiger, Y. Ben-Yoseph, and R. Arnon, Purification of human hexosaminidase A and B by affinity chromatography, FEBS Lett. 45:276-281 (1974).
D. J. Mahuran, and J. A. Lowden, The subunit and polypeptide structure of hexosaminidase from human placenta, Can. J. Biochem. 58:287-294 (1980).
D. J. Mahuran, F. Tsui, R. A. Gravel, and J. A. Lowden, Evidence for two dissimilar polypeptide chains in the β2 subunit of hexosaminidase, Proc. Natl. Acad. Sci. (U.S.A.). 79:1602-1605 (1982).
A. Hasilik, and E. F. Neufeld, Biosynthesis of lysosomal enzymes in fibroblasts: synthesis as precursors of higher molecular weight, J. Biol. Chem. 255:4937-4945 (1980).
F. Tsui, D. J. Mahuran, J. A. Lowden, T. Mosmann, and R. A. Gravel, Characterization of polypeptides serilogically and structurally related to hexosaminidase in cultured fibroblasts, J. Clin. Invest. 71:965-973 (1983).
R. L. Prioa, and E. Neufeld, Synthesis of β-hexosaminidase in a cell-free translation and in intact fibroblasts: an insoluble precursor a-chain in a rare form of Tay-Sachs disease, Proc. Natl. Acad. Sci. (U.S.A). 79:6360-6364 (1982).
R. L. Proia, A. d’Azzo, and F. Neufeld, Association of a-and β-subunits during the biosynthesis of β-hexosaminidase in cultured fibroblasts, J. Biol. Chem. 259:3350-3354 (1984).
L. Lang, M. Reitman, J. Tang, R. M. Roberts, and S. Kornfeld, Lysosomal enzme phosphorylation: Recognition of a protein-dependent determinant allows specific phosphorolation of oligosaccharides present on lysosomal enzymes, J. Biol. Chem. 259:14663-14671 (1984).
M. Kozak, Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs, Nucleic Acid Research. 12:857-872 (1984).
G. von Heijne, Patterns of amino acids near signal-sequence cleavage sites, Eur. J. Biochem. 133:17-27(19831
G. von Heijne, A new method for predicting signal sequence cleavage sites, Nucleic Acids Res. 14:4683-4690 (1986).
J. P. Segrest, and R. L. Jackson, Molecular weight determination of glycoproteins by Polyacrylamide gel electrophoresis in sodium dodecyl sulfate, Methods Enzvmol. 28:54-61 (1972).
D. R. Lynch, and S. H. Snyder, Neuropeptides: Multipal molecular forms, metabolic pathways, and receptors; Annual Review of Biochemistry. 55:773-799 (1986).
H. Freeze, B. Gerger, and A. L. Miller, Carbohydrate composition of human placental Is acetylhexosaminidase A and B, Biochem. J. 177:749-752 (1979).
B. F. O’Dowd, D. Mahuran, D. Cumming, and J. A. Lowden, Characterization by nuclear magnetic resonance of the concanavalin A binding oligosaccharides on the βb chain of placental β-hexosaminidase B: lectin binding to the separated polypeptide chains of hexosaminidase A and B, Can. J. Biochem. Cell Biol. 63:723-729 (1985).
T. Tai, K. Yamashita, and A. Kobata, The substrate specificities of endo-β-N-acetylglucosaminidase CH and H, Biochem. Biophys. Res. Commun. 78:434-441 (1977).
T. Takahashi, P. G. Schmidt, and J. Tang, novel carbohydrate structures of cathepsin B from porcine spleen. J. Biol. Chem. 259:6059-6062 (1984).
R. Kornfeld, and S. Kornfeld, Assenbly of asparagine-linked oligosaccharides, Ann. Rev. Biochem. 54:631-664 (1985).
J. Gamier, D. J. Osguthorpe, and B. Robson, Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins, J. Mol. BioL 120:97-120 (1978).
A. Hasilik, K. von Figura, E. Conzelmann, H. Nehrkorn, and K. Sandhoff, Lysosomal enzyme precursors in human fibroblasts, Eur. J. Biochem. 125:317-321 (1982).
D. Goldberg, C. Gabel, and S. Kornfeld, Processing of lysosomal enzyme oligosaccharide units, In: “Lysosomes in Pathology and Biology”, ed. J. T. Dingle, R. T. Dean, Elsevier, North-Holland, New York, pp. 45-62 (1984).
R. Couso, L. Lang, R. M. Roberts, and S. Kornfeld, Phosphorylation of the oligosaccharide of uteroferrin by UDP-GlcNAc: glycoprotein N-acetylglucosamine-1-phosphotransferases from rat liver, Acanthamoeba castellani, and dictyostelium discoideum requires a 1,2-linked mannose residues. J. Biol. Chem. 261:6326–6331 (1986).
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© 1988 Plenum Press, New York
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Mahuran, D.J., Gravel, R. (1988). The Molecular Biology of β-Hexosaminidase: Localization of the Proteolytic Processing and Carbohydrate Containing Sites. In: Salvayre, R., Douste-Blazy, L., Gatt, S. (eds) Lipid Storage Disorders. NATO ASI Series, vol 150. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1029-7_26
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DOI: https://doi.org/10.1007/978-1-4613-1029-7_26
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