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The methylation pathway, also known as one-carbon metabolism, is a fundamental biochemical network that facilitates the transfer of methyl groups to DNA, proteins, and lipids (Ducker & Rabinowitz, 2017). It integrates the folate and methionine cycles to produce S-adenosylmethionine (SAM), the universal methyl donor required for epigenetic regulation and cellular maintenance (Lu, 2000). This pathway is vital for DNA synthesis, repair, and the regulation of gene expression through DNA and histone methylation (Moore et al., 2013). Dysregulation of the pathway is a hallmark of various diseases, particularly cancer, where it contributes to oncogene activation or tumor suppressor silencing (Jones & Baylin, 2002). It is also critically involved in cardiovascular health by managing homocysteine levels and in neurological function through the synthesis of neurotransmitters like serotonin and dopamine (Selhub, 1999). Pharmacological modulation of the pathway includes the use of DNA methyltransferase inhibitors for treating myelodysplastic syndromes and folate antagonists for cancer and autoimmune diseases (Gore et al., 2006).
Inhibition of DNA methyltransferases (DNMTs), inhibition of histone methyltransferases (HMTs), inhibition of folate metabolism enzymes (e.g., DHFR), and provision of methyl donors or metabolic precursors.
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