title: G(M1)-ganglioside degradation and biosynthesis in human and murine G(M1)-gangliosidosis.
abstract: BACKGROUND
  Gangliosides are building blocks of cell membranes and their biosynthesis and degradation have been extensively studied in the past. Regulation of the metabolism of these glycolipids controls fundamental cell functions. G(M1)-gangliosidosis, a neurodegenerative glycosphingolipid storage disease, is caused by deficiency of lysosomal beta-galactosidase with consequent disruption of the normal degradative pathway of G(M1)-ganglioside. We studied the impact of G(M1)-ganglioside accumulation on its biosynthetic enzyme in cells and tissues from human patients and from the G(M1)-gangliosidosis mouse model.
  
  
  METHODS
  We tested the qualitative and quantitative pattern of gangliosides by thin layer chromatography and N-acetylneuraminic acid dosage, respectively. Regulation of G(M1)-ganglioside biosynthesis was evaluated by G(M1) synthase assay in human and murine samples.
  
  
  RESULTS
  G(M1)-ganglioside accumulation has an inhibitory effect on the human but not on the mouse G(M1) synthase. We present evidence that G(M1) synthase activity in human and murine cells are regulated by different mechanisms.
  
  
  CONCLUSIONS
  Alternative pathways in the mouse may account for these results and possibly explain some of the phenotypical differences between the human and mouse forms of this disorder.
authors.affiliation: Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Renata
authors.initials: R
authors.lastname: Sano
authors.forename: Vera M T
authors.initials: VM
authors.lastname: Trindade
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tessitore
authors.forename: Alessandra
authors.initials: A
authors.lastname: d'Azzo
authors.forename: Matheus B
authors.initials: MB
authors.lastname: Vieira
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.forename: Janice C
authors.initials: JC
authors.lastname: Coelho
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002855:Chromatography, Thin Layer; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000737:chemistry; D005677:G(M1) Ganglioside / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism*; D016537:Gangliosidosis, GM1 / Q000378:metabolism*; D006602:Hexosyltransferases / Q000378:metabolism; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype
chemical_list: D005677:G(M1) Ganglioside; C014866:G(M1)ganglioside synthetase; D006602:Hexosyltransferases