SCOPE: 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. METHODS AND 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. CONCLUSION: 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.
SCOPE: 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. METHODS AND 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. CONCLUSION: 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: Caitlin G Howe; Megan M Niedzwiecki; Megan N Hall; Xinhua Liu; Vesna Ilievski; Vesna Slavkovich; Shafiul Alam; Abu B Siddique; Joseph H Graziano; Mary V Gamble Journal: J Nutr Date: 2014-03-05 Impact factor: 4.798
Authors: Jin Gao; Catherine M Cahill; Xudong Huang; Joshua L Roffman; Stefania Lamon-Fava; Maurizio Fava; David Mischoulon; Jack T Rogers Journal: Neurotherapeutics Date: 2018-01 Impact factor: 7.620
Authors: Mara Dierssen; Marta Fructuoso; María Martínez de Lagrán; Marzia Perluigi; Eugenio Barone Journal: Front Neurosci Date: 2020-07-08 Impact factor: 4.677