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Partitioning of One-Carbon Units in Folate and Methionine Metabolism Is Essential for Neural Tube Closure.

Leung, K-Y; Pai, YJ; Chen, Q; Santos, C; Calvani, E; Sudiwala, S; Savery, D; ... Greene, NDE; + view all (2017) Partitioning of One-Carbon Units in Folate and Methionine Metabolism Is Essential for Neural Tube Closure. Cell Rep , 21 (7) pp. 1795-1808. 10.1016/j.celrep.2017.10.072. Green open access

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Abstract

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.

Type: Article
Title: Partitioning of One-Carbon Units in Folate and Methionine Metabolism Is Essential for Neural Tube Closure.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2017.10.072
Publisher version: https://doi.org/10.1016/j.celrep.2017.10.072
Language: English
Additional information: © 2017 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Gldc, Mthfr, eye, folic acid, glycine cleavage system, neural tube defects, non-ketotic hyperglycinemia, one-carbon metabolism, spina bifida
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10038807
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