Partitioning of one-carbon units in folate and methionine metabolism is essential for neural tube closure
More about Open Access at the CrickAuthors list
Kit-Yi Leung Yun Jin Pai Qiuying Chen Chloe Santos Enrica Calvani Sonia Sudiwala Dawn Savery Markus Ralser Steven S Gross Andrew J Copp Nicholas DE GreeneAbstract
Abnormal folate one-carbon metabolism (FOCM) is implicated in neural tube defects (NTDs), severe malformations of the nervous system. MTHFR mediates unidirectional transfer of methyl groups from the folate cycle to the methionine cycle and, therefore, represents a key nexus in partitioning one-carbon units between FOCM functional outputs. Methionine cycle inhibitors prevent neural tube closure in mouse embryos. Similarly, the inability to use glycine as a one-carbon donor to the folate cycle causes NTDs in glycine decarboxylase (Gldc)-deficient embryos. However, analysis of Mthfr-null mouse embryos shows that neither S-adenosylmethionine abundance nor neural tube closure depend on one-carbon units derived from embryonic or maternal folate cycles. Mthfr deletion or methionine treatment prevents NTDs in Gldc-null embryos by retention of one-carbon units within the folate cycle. Overall, neural tube closure depends on the activity of both the methionine and folate cycles, but transfer of one-carbon units between the cycles is not necessary.
Journal details
Journal Cell Reports
Volume 21
Issue number 7
Pages 1795-1808
Available online
Publication date
Full text links
Publisher website (DOI) 10.1016/j.celrep.2017.10.072
Figshare View on figshare
Europe PubMed Central 29141214
Pubmed 29141214
Keywords
Related topics
Type of publication