Abstract
Natural substrates of many lysosomal hydrolases are highly hydrophobic. While the reactions can proceed in vitro when appropriate detergents are included in the assay mixture, these enzymes must function in vivo without artificial detergents of high concentrations often required for in vitro reactions. Since the first report of an endogenous activator protein for hydrolysis of sulfatide by arylsulfatase A by Mehl and Jatzkewitz (1), so-called natural activator proteins have been described for glucosylceramidase (2–4), GM1-ganglioside β-galactosidase (5,6), GM2-ganglioside N-acetyl-β-galactosaminidase (7,8), sulfatide sulfatase (1,9), and ceramide trihexoside α-galactosidase (10). The physiological significance of at least some of these natural activators has been convincingly indicated by the existence of genetic disorders in which activators are defective, such as GM2-gangliosidosis AB variant (7) or metachromatic leukodystrophy due to activator deficiency (l1).
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References
E. Mehl and H. Jatzkewitz, Eine Cerebrosidsulfatase aus Schweineniere, Hoppe-Seyler’s Z. Physiol. Chem. 339: 260 (1964).
M. W. Ho and J. S. O’Brien, Gaucher’s disease: Deficiency of “acid” 0-glucosidase and reconstitution of enzyme activity in vitro, Proc. Nat. Acad. Sci., U.S.A. 68: 2810 (1971).
M. W. Ho, J. S. O’Brien, N. S. Radin and J. S. Erickson, Glucocerebrosidase: Reconstitution from macromolecular components, Biochem. J. 131: 173 (1973)
M. W. Ho and N. D. Light, Glucocerebrosidase: Reconstitution from macromolecular components depends on acidic phospholipids, Biochem. J. 136: 821 (1973).
S. C. Li, C. C. Wan, M. Y. Mazzotta, and Y. T. Li, Requirement of an activator for the hydrolysis of sphingoglycolipids by glycosidases of human liver, Carbohydrate Res. 34: 189 (1974).
S. C. Li and Y. T. Li, An activator stimulating the enzymic hydrolysis of sphingoglycolipids, J. Biol. Chem. 251: 1159 (1976).
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. Nat. Acad. Sci., U.S.A. 75: 3937 (1978).
E. Conzelmann and K. Sandhoff, Purification and characterization of an activator protein for the degradation of glycolipids GM2 and GA2 by hexosaminidase A, Hoppe-Seyler’s Z. Physiol. Chem. 360: 1837 (1979).
H. Jatzkewitz and K. Stinhoff, An activator of cerebroside sulfatase in human normal liver and in cases of congenital metachromatic leukodystrophy, FEBS Lett. 32: 129 (1973).
S. Gârtner, E. Conzelmann and K. Sandhoff, Activator protein for the degradation of globotriaosyl ceramide by human a-galactosidase, J. Biol. Chem. 258: 12378 (1983).
R. L. Stevens, A. L. Fluharty, H. Kihara, M. M. Kaback, L. J. Shapiro, B. Marsh, K. Sandhoff and G. Fischer, Cerebroside sulfatase activator deficiency induced metachromatic leukodystrophy, Am. J. Human Genet. 33, 900 (1981).
P. G. Pentchev and R. O. Brady, The effect of a heat-stable factor in human spleen on glucocerebrosidase and acid β-glucosidase activities, Biochim. Biophys. Acta 297: 491 (1973).
S. P. Peters, C. S. Coffee, R. H. Glew, R. E. Lee, D. A. Wenger, S. C. Li and Y. T. Li, Isolation of heat-stable glucocerebrosidase activators from the spleens of three variants of Gaucher’s disease, Arch. Biochem. Biophys. 183: 290 (1977).
S. P. Peters, P. Coyle, C. S. Coffee, R. H. Glew, M. S. Kuhlenschmidt, L. Rosenfeld and Y. C. Lee, Purification and properties of a heat-stable glucocerebrosidase activating factor from control and Gaucher spleen, J. Biol. Chem. 252: 563 (1977).
S. L. Berent and N. S. Radin, Mechanism of activation of glucocerebrosidase by co-glucosidase (glucosidase activator protein), Biochim. Biophys. Acta 664: 572 (1981).
A. Basu, R. H. Glew, L. B. Daniels and L. S. Clark, Activators of spleen glucocerebrosidase from controls and patients with various forms of Gaucher’s disease, J. Biol. Chem. 259: 1714 (1984).
D. A. Wenger, M. Sattler and S. Roth, A protein activator of galactosylceramide ß-galactosidase, Biochim. Biophys. Acta 712: 639 (1982).
H. Christomanou, Niemann-Pick disease, type C: Evidence for the deficiency of an activating factor stimulating sphingomyelin and glucocerebroside degradation, Hoppe Seyler’s Z. Physiol. Chem. 361: 1489 (1980).
A. M. Vaccaro, M. Muscillo, E. Gallozzi, R. Salvioli, M. Tatti and K. Suzuki, An endogenous activator protein in human placenta for enzymatic degradation of glucosylceramide, Biochim. Biophys. Acta 836: 157 (1985).
M. C. McMaster, Jr. and N. S. Radin, Preparation of [6–3H]gluco-cerebroside, J. Labelled Comp. Radiopharmaceut. 13: 353 (1977).
N. S. Radin, L. Hof, R. M. Bradley and R. O. Brady, Lactosylceramide galactosidase: Comparison with other sphingolipid hydrolases in developing rat brain, Brain Res. 14: 497 (1969).
K. Suzuki, Globoid cell leukodystrophy (Krabbe disease) and GM1-gangliosidosis, in “Practical Enzymology of the Sphingolipidoses”, R. H. Glew and S. P. Peters, eds., pp. 101–136, Alan R. Liss, New York (1977).
F. S. Furbish, H. E. Blair, J. Shiloach, P. G. Pentchev and R. O. Brady, Enzyme replacement therapy in Gaucher’s disease: Large-scale purification of glucocerebrosidase suitable for human administration, Proc. Nat. Acad. Sci., U.S.A. 74: 3560 (1977).
M. M. Bradford, A rapid and sensitive method for the quantitation of microgram quantity of protein utilizing the principle of protein dye binding, Anal. Biochem. 72: 248 (1976).
R. H. Glew and C. S. Coffee, Calmodulin and paralbumin: Activators of human liver glucocerebrosidase, Arch. Biochem. Biophys. 229: 55 (1984).
D. A. Wenger and S. Roth, Homozygote and heterozygote identification, in “Gaucher Disease: A Century of Delineation and Research”, R. J. Desnick, S. Gatt and G. A. Grabowski, eds., pp. 551–572, Alan R. Liss, New York (1982).
S. S. Iyer, S. L. Berent and N. S. Radin, The cohydrolases in human spleen that stimulate glucosyl ceramide β-glucosidase, Biochim. Biophys. Acta 748: 1 (1983).
D. A. Wenger, M. Sattler, C. Clark and C. Wharton, I-Cell disease: Activities of lysosomal enzymes toward natural and synthetic substrates, Life Sci. 19: 413 (1976).
S. P. Peters, P. Coyle and R. H. Glew, Differentiation of β-glucocerebrosidase from β-glucosidase in human tissues using sodium taurocholate, Arch. Biochem. Biophys. 175: 569 (1976).
B. Shafit-Zagardo and B. M. Turner, Human β-glucosidase: Inhibition by sulphates and purification by affinity chromatography on dextran-sulphate-Sepharose, Biochim. Biophys. Acta 659: 7 (1981).
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© 1986 Plenum Press, New York
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Vaccaro, A.M., Muscillo, M., Gallozzi, E., Salvioli, R., Tatti, M., Suzuki, K. (1986). A New Glucosylceramidase Activator in Human Placenta. In: Freysz, L., Dreyfus, H., Massarelli, R., Gatt, S. (eds) Enzymes of Lipid Metabolism II. NATO ASI Series, vol 116. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5212-9_49
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