Inhibition of transmethylation disturbs neurulation in chick embryos

Lydia A Afman, Henk J Blom, Marie-Jose Drittij, Madeleine R Brouns, Henny W M van Straaten

Research output: Contribution to JournalArticleAcademicpeer-review


Periconceptional folic acid supplementation can reduce the occurrence of neural tube defects. A low folate status will result in reduced remethylation of homocysteine (Hcy) to methionine and, subsequently, in a rise of Hcy levels. Indeed, elevated Hcy concentrations have been reported in mothers of children with neural tube defects. In our previous study, we showed that treatment of chick embryos with Hcy resulted in a delay of neural tube closure in an in vitro model. In the present study, we examined whether this effect of Hcy is due to inhibition of transmethylation via elevation of S-adenosylhomocysteine (AdoHcy). Transmethylation involves methylation of DNA, RNA and proteins by donation of a methyl group from S-adenosylmethionine (AdoMet). After application of inhibitors of S-adenosylhomocysteine hydrolase and of methionine adenosyltransferase, a delay of anterior neuropore closure, comparable to that observed after Hcy treatment, was observed. The changes in AdoMet and AdoHcy concentrations confirmed the inhibition of S-adenosylhomocysteine hydrolase or methionine adenosyltransferase, respectively, and the AdoMet/AdoHcy ratio was decreased in all cases, indicating reduced transmethylation. Moreover, the inhibition of methionine adenosyltransferase was prevented by pretreatment with methionine. This study, therefore, indicates that the Hcy-induced delay of the neural tube closure is caused by the inhibition of transmethylation via elevation of AdoHcy levels and a reduction of the AdoMet/AdoHcy ratio.

Original languageEnglish
Pages (from-to)59-65
Number of pages7
JournalDevelopmental Brain Research
Issue number1-2
Publication statusPublished - 8 Aug 2005
Externally publishedYes


  • Adenosine/pharmacology
  • Adenosylhomocysteinase/metabolism
  • Animals
  • Chick Embryo/physiology
  • Cycloleucine/pharmacology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Embryonic Development/drug effects
  • Homocysteine/pharmacology
  • Methylation/drug effects
  • Models, Biological
  • Nervous System/embryology
  • Organogenesis/drug effects
  • S-Adenosylhomocysteine/metabolism
  • Time Factors
  • Tubercidin/pharmacology


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