Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1975 Jan;72(1):240–244. doi: 10.1073/pnas.72.1.240

An electrophoretic variant of beta-galactosidase with altered catalytic properties in a patient with GM1 gangliosidosis.

A G Norden, J S O'Brien
PMCID: PMC432279  PMID: 804170

Abstract

In nine patients with GM1 gangliosidosis, liver ganglioside GM1 beta-galactosidase (EC 3.2.1.23) activity ranged from less than 0.01% to 0.05% of normal. In a tenth patient's liver, much higher activity was found (0.5% of normal). In this patient the residual enzyme had the same molecular weight as beta-galactosidase A, the major form of beta-galactosidase of normal human liver. No activity was found that corresponded to beta-galactosidase B, the minor form of human liver beta-galactosidase. On starch gel electrophoresis, the patient's enzyme migrated less anodally than normal beta-galactosidase A, both before and after treatment with neuraminidase. Beta-Galactosidase from the patient had a Km that was higher then normal; 5-fold higher with ganglioside GM1 and 2-fold higher with 4-methylumbelliferyl beta-galactoside. The patient's enzyme crossreacted immunologically with normal beta-galactosidase A and had about 100-fold more antigenic activity per unit catalytic activity than the normal enzyme. The results indicate that in this patient a beta-galactosidase A protein with altered charge and altered catalytic properties was present in relatively normal amounts, the first electrophoretic variant reported for a patient with a lysosomal hydrolase deficiency.

Full text

PDF
240

Images in this article

243Image
on p.243

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baker H. J., Lindsey J. R. Animal model: feline GM1 gangliosidosis. Am J Pathol. 1974 Mar;74(3):649–652. [PMC free article] [PubMed] [Google Scholar]
  2. Chou L., Kaye C. I., Nadler H. L. Brain beta-galactosidase and gm1 gangliosidosis. Pediatr Res. 1974 Feb;8(2):120–125. doi: 10.1203/00006450-197402000-00009. [DOI] [PubMed] [Google Scholar]
  3. Feldges A., Müller H. J., Bühler E., Stalder G. GM1-gangliosidosis. I. Clinical aspects and biochemistry. Helv Paediatr Acta. 1973 Dec;28(6):511–519. [PubMed] [Google Scholar]
  4. Goldstone A., Konecny P., Koenig H. Lysosomal hydrolases: Conversion of acidic to basic forms by neuraminidase. FEBS Lett. 1971 Feb 12;13(1):68–72. doi: 10.1016/0014-5793(71)80667-1. [DOI] [PubMed] [Google Scholar]
  5. Ho M. W., Cheetham P., Robinson D. Hydrolysis of GM1-ganglioside by human liver beta-galactosidase isoenzymes. Biochem J. 1973 Oct;136(2):351–359. doi: 10.1042/bj1360351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ho M. W., O'Brien J. S. Differential effect of chloride ions on -galactosidase isoenzymes: a method for separate assay. Clin Chim Acta. 1971 May;32(3):443–450. doi: 10.1016/0009-8981(71)90446-3. [DOI] [PubMed] [Google Scholar]
  7. Ho M. W., Seck J., Schmidt D., Veath M. L., Johnson W., Brady R. O., O'Brien J. S. Adult Gaucher's disease: kindred studies and demonstration of a deficiency of acid beta-glucosidase in cultured fibroblasts. Am J Hum Genet. 1972 Jan;24(1):37–45. [PMC free article] [PubMed] [Google Scholar]
  8. King J. L. The probability of electrophoretic idendity of proteins as a function of amino acid divergence. J Mol Evol. 1973 Nov 27;2(4):317–322. doi: 10.1007/BF01654099. [DOI] [PubMed] [Google Scholar]
  9. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  10. Norden A. G., O'Brien J. S. Binding of human liver beta-galactosidases to plant lectins insolubilized on agarose. Biochem Biophys Res Commun. 1974 Jan;56(1):193–198. doi: 10.1016/s0006-291x(74)80333-5. [DOI] [PubMed] [Google Scholar]
  11. Norden A. G., O'Brien J. S. Ganglioside GM1 beta-galactosidase: studies in human liver and brain. Arch Biochem Biophys. 1973 Nov;159(1):383–392. doi: 10.1016/0003-9861(73)90465-7. [DOI] [PubMed] [Google Scholar]
  12. Norden A. G., Tennant L. L., O'Brien J. S. GM1 ganglioside beta-galactosidase. A. Purification and studies of the enzyme from human liver. J Biol Chem. 1974 Dec 25;249(24):7969–7976. [PubMed] [Google Scholar]
  13. O'Brien J. S., Fillerup D. L., Mead J. F. Quantification and fatty acid and fatty aldehyde composition of ethanolamine, choline, and serine glycerophosphatides in human cerebral grey and white matter. J Lipid Res. 1964 Jul;5(3):329–338. [PubMed] [Google Scholar]
  14. O'Brien J. S., Ho M. W., Veath M. L., Wilson J. F., Myers G., Opitz J. M., ZuRhein G. M., Spranger J. W., Hartmann H. A., Haneberg B. Juvenile GM 1 gangliosidosis: clinical, pathological, chemical and enzymatic studies. Clin Genet. 1972;3(6):411–434. doi: 10.1111/j.1399-0004.1972.tb01476.x. [DOI] [PubMed] [Google Scholar]
  15. SMITHIES O. An improved procedure for starch-gel electrophoresis: further variations in the serum proteins of normal individuals. Biochem J. 1959 Mar;71(3):585–587. doi: 10.1042/bj0710585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Singer H. S., Schafer I. A. Clinical and enzymatic variations in G M1 generalized gangliosidosis. Am J Hum Genet. 1972 Jul;24(4):454–463. [PMC free article] [PubMed] [Google Scholar]
  17. Taori G. M., Basu D. K., Chandi S., Raman P. T., Abraham J., Leelavathy R., Job C. K. GM1 gangliosidosis. J Neurol Sci. 1974 Jan;21(1):77–92. doi: 10.1016/0022-510x(74)90108-7. [DOI] [PubMed] [Google Scholar]
  18. Touster O. Some aspects of the cellular biochemistry of lysosomal and related glycosidases. Mol Cell Biochem. 1973 Dec 15;2(2):169–177. doi: 10.1007/BF01795471. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES