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Nutriepigenetic regulation by folate–homocysteine–methionine axis: a review

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Abstract

Although normally folic acid is given during pregnancy, presumably to prevent neural tube defects, the mechanisms of this protection are unknown. More importantly it is unclear whether folic acid has other function during development. It is known that folic acid re-methylates homocysteine (Hcy) to methionine by methylene tetrahydrofolate reductase-dependent pathways. Folic acid also generates high-energy phosphates, behaves as an antioxidant and improves nitric oxide (NO) production by endothelial NO synthase. Interestingly, during epigenetic modification, methylation of DNA/RNA generate homocysteine unequivocally. The enhanced overexpression of methyl transferase lead to increased yield of Hcy. The accumulation of Hcy causes vascular dysfunction, reduces perfusion in the muscles thereby causing musculopathy. Another interesting fact is that children with severe hyperhomocysteinaemia (HHcy) have skeletal deformities, and do not live past teenage. HHcy is also associated with the progeria syndrome. Epilepsy is primarily caused by inhibition of gamma-amino-butyric-acid (GABA) receptor, an inhibitory neurotransmitter in the neuronal synapse. Folate deficiency leads to HHcy which then competes with GABA for binding on the GABA receptors. With so many genetic and clinical manifestations associated with folate deficiency, we propose that folate deficiency induces epigenetic alterations in the genes and thereby results in disease.

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Authors and Affiliations

  1. Department of Biochemistry, Sir Ganga Ram Hospital, New Delhi, India

    Seema Bhargava

  2. Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, KY, USA

    Seema Bhargava & S. C. Tyagi

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  1. Seema Bhargava
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  2. S. C. Tyagi
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Correspondence to Seema Bhargava.

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Bhargava, S., Tyagi, S.C. Nutriepigenetic regulation by folate–homocysteine–methionine axis: a review. Mol Cell Biochem 387, 55–61 (2014). https://doi.org/10.1007/s11010-013-1869-2

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  • DOI: https://doi.org/10.1007/s11010-013-1869-2

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