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Journal List > Proc Natl Acad Sci U S A > v.75(8); Aug 1978

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Proc Natl Acad Sci U S A. 1978 August; 75(8): 3979–3983.
PMCID: PMC392913
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AB variant of infantile GM2 gangliosidosis: deficiency of a factor necessary for stimulation of hexosaminidase A-catalyzed degradation of ganglioside GM2 and glycolipid GA2.
E Conzelmann and K Sandhoff
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Abstract
Human kidney extracts heated to 60 degrees and devoid of hexosaminidase activity (2-acetamido-2-deoxy-beta-D-glucoside acetamidodeoxyglucohydrolase EC 3.2.1.30) stimulate more than 20-fold the hexosaminidase A-catalyzed degradation of ganglioside GM2 and of glycolipid GA2, the neuronal storage compounds of GM2 gangliosidosis. The stimulating factor of this extract, which is labile at temperatures above 60 degrees, is also present in kidney extracts from patients with infantile GM2 gangliosidosis having a deficiency of hexosaminidase A (Tay-Sachs disease, variant B) and a deficiency of hexosaminidases A and B (variant 0). Evidence is presented that this factor is defective in the AB-variant of infantile GM2 gangliosidosis which is characterized by an accumulation of glycolipids GM2 and GA2 despite the fact that the degrading enzymes, hexosaminidases A and B, retain normal activity levels. Thus, variant AB is an example of a fatal lipid storage disease that is caused not by a defect of a degrading enzyme but rather by a defective factor necessary for the interaction of lipid substrates and the water-soluble hydrolase.
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Selected References
These references are in PubMed. This may not be the complete list of references from this article.
  • Sandhoff K. The biochemistry of sphingolipid storage diseases. Angew Chem Int Ed Engl. 1977 May;16(5):273–285. [PubMed]
  • Okada S, O'Brien JS. Tay-Sachs disease: generalized absence of a beta-D-N-acetylhexosaminidase component. Science. 1969 Aug 15;165(894):698–700. [PubMed]
  • Sandhoff K. Variation of beta-N-acetylhexosaminidase-pattern in Tay-Sachs disease. FEBS Lett. 1969 Aug;4(4):351–354. [PubMed]
  • Sandhoff K, Conzelmann E, Nehrkorn H. Specificity of human liver hexosaminidases A and B against glycosphingolipids GM2 and GA2. Purification of the enzymes by affinity chromatography employing specific elution. Hoppe Seylers Z Physiol Chem. 1977 Jul;358(7):779–787. [PubMed]
  • Sandhoff K, Andreae U, Jatzkewitz H. Deficient hexosaminidase activity in an exceptional case of Tay-Sachs disease with additional storage of kidney globoside in visceral organs. Pathol Eur. 1968;3(2):278–285. [PubMed]
  • Sandhoff K, Harzer K, Wässle W, Jatzkewitz H. Enzyme alterations and lipid storage in three variants of Tay-Sachs disease. J Neurochem. 1971 Dec;18(12):2469–2489. [PubMed]
  • Geiger B, Arnon R. Chemical characterization and subunit structure of human N-acetylhexosaminidases A and B. Biochemistry. 1976 Aug 10;15(16):3484–3493. [PubMed]
  • Conzelmann E, Sandhoff K, Nehrkorn H, Geiger B, Arnon R. Purification, biochemical and immunological characterisation of hexosaminidase A from variant AB of infantile GM2 gangliosidosis. Eur J Biochem. 1978 Mar;84(1):27–33. [PubMed]
  • Fischer G, Jatzkewitz H. The activator of cerebroside sulphatase. Purification from human liver and identification as a protein. Hoppe Seylers Z Physiol Chem. 1975 May;356(5):605–613. [PubMed]
  • Ho MW, O'Brien JS. Gaucher's disease: deficiency of 'acid' -glucosidase and reconstitution of enzyme activity in vitro. Proc Natl Acad Sci U S A. 1971 Nov;68(11):2810–2813. [PubMed]
  • Hechtman P. Characterization of an activating factor required for hydrolysis of Gm2 ganglioside catalyzed by hexosaminidase A. Can J Biochem. 1977 Apr;55(4):315–324. [PubMed]
  • O'Brien JS, Norden GW, Miller AL, Frost RG, Kelly TE. Ganglioside GM2 N-acetyl-beta-D-galactosaminidase and asialo GM2 (GA2) N-acetyl-beta-D-galactosaminidase; studies in human skin fibroblasts. Clin Genet. 1977 Mar;11(3):171–183. [PubMed]
  • LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed]
  • Geiger B, Arnon R, Sandhoff K. Immunochemical and biochemical investigation of hexosaminidase S. Am J Hum Genet. 1977 Sep;29(5):508–522. [PubMed]
  • Hechtman P, LeBlanc D. Purification and properties of the hexosaminidase A-activating protein from human liver. Biochem J. 1977 Dec 1;167(3):693–701. [PubMed]
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