title: Blood biomarkers of methylation in Down syndrome and metabolic simulations using a mathematical model.
abstract: METHODS
  The study tests the metabolites of the methylation cycle in individuals with Down syndrome (DS) and applies a mathematical model in order to change this cycle by nutritional factors.
  
  
  RESULTS
  We measured concentrations of the metabolites related to the methylation cycle in the blood of 35 young individuals with DS and 47 controls of comparable age. Moreover, we applied a mathematical model to learn more about the regulation of the methylation cycle in DS. Concentrations of cystathionine, cysteine, betaine, choline, dimethylglycine, S-adenosylhomocysteine (SAH), S-adenosylmethionine (SAM), and holotranscobalamin were significantly higher in DS compared to the controls. The median SAM/SAH ratio was lower in DS and that of methionine and reduced glutathione did not differ significantly between the groups. The mathematical model showed that enhanced methionine turnover and accelerated Hcy-remethylation might explain the shift in the methylation cycle in DS.
  
  
  CONCLUSIONS
  In addition to the DS-related excess of cystathionine beta synthase (CBS) activity, increases in the activities of MS and betaine homocysteine methyl transferase, and in methionine input were necessary to account for the changes in metabolite levels observed in DS. A low-methionine diet might offer a perspective for reversing the metabolic imbalance in DS, but this awaits clinical investigations.
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Saarland University, Medical Centre, Homburg, Germany. rima.obeid@uniklinikum-saarland.de
authors.forename: Rima
authors.initials: R
authors.lastname: Obeid
authors.forename: Kathrin
authors.initials: K
authors.lastname: Hartmuth
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Herrmann
authors.forename: Ludwig
authors.initials: L
authors.lastname: Gortner
authors.forename: Tilman R
authors.initials: TR
authors.lastname: Rohrer
authors.forename: Jürgen
authors.initials: J
authors.lastname: Geisel
authors.forename: Michael C
authors.initials: MC
authors.lastname: Reed
authors.forename: H Frederik
authors.initials: HF
authors.lastname: Nijhout
mesh_terms: D000293:Adolescent; D000328:Adult; D001622:Betaine / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002794:Choline / Q000097:blood; D003540:Cystathionine / Q000097:blood; D003545:Cysteine / Q000097:blood; D004314:Down Syndrome / Q000097:blood*; D005260:Female; D005978:Glutathione / Q000097:blood; D006801:Humans; D007223:Infant; D008297:Male; D008715:Methionine / Q000097:blood; D008745:Methylation; D008962:Models, Theoretical; D012435:S-Adenosylhomocysteine / Q000097:blood; D012436:S-Adenosylmethionine / Q000097:blood; D012521:Sarcosine / Q000031:analogs & derivatives / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D003540:Cystathionine; D001622:Betaine; C025138:dimethylglycine; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D008715:Methionine; D005978:Glutathione; D003545:Cysteine; D002794:Choline; D012521:Sarcosine