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Lifetime requirement of the methionine cycle for neuronal development and maintenance

Shea, Thomas B.a,b; Rogers, Eugenea,c

Current Opinion in Psychiatry: March 2014 - Volume 27 - Issue 2 - p 138–142
doi: 10.1097/YCO.0000000000000046

Purpose of review Nutrition exerts a pervasive impact on normal and pathological conditions of the nervous system. One critical pathway is the methionine cycle, in which folate and B12 convert homocysteine to methionine, which is in turn converted to S-adenosyl methionine (SAM; the major methyl donor). As a consequence of methylation, however, SAM is converted to the neurotoxin homocysteine and must be excreted or drawn back into the methionine cycle, which requires additional folate and B12. Dietary or genetic folate deficiency impairs this cycle, leading to developmental disorders, including those of the nervous system.

Recent findings Folate and SAM exert profound epigenetic effects via DNA and histone methylation. Maternal supplementation during pregnancy has fostered an increase in individuals harboring genetic polymorphisms that compromise folate usage. Such individuals harbor a lifetime requirement for additional dietary folate, often not met beyond peri/postnatal periods. Herein, we consider the potential link of failure to meet this additional requirement to early and age-related cognitive compromise.

Summary Compromises in the methionine cycle can manifest as a spectrum of disorders throughout life. These considerations underscore how prenatal nutritional supplementation can alleviate developmental disorders by inadvertently establishing latent conditions that, in the absence of continued supplementation, may lead to age-related cognitive decline.

aCenter for Neuroscience

bDepartment of Biological Sciences

cClinical Laboratory Science, University of Massachusetts Lowell, Lowell, Massachusetts, USA

Correspondence to Thomas B. Shea, Center for Neuroscience, Department of Biological Sciences, Lowell, MA 01854, USA. Tel: +1 978 934 2881; fax: +1 9780 934 3044; e-mail:

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