Epigenetic and metabolic pathways

The term Epigenetic and metabolic pathways refers to the complex bidirectional communication between cellular metabolism and the epigenetic machinery that regulates gene expression. Metabolic intermediates, such as acetyl-CoA, S-adenosylmethionine (SAM), and alpha-ketoglutarate, serve as indispensable substrates or cofactors for enzymes that modify DNA and histones (Lu & Thompson, 2012, Cell Metabolism). Consequently, changes in the metabolic state of a cell can directly alter the epigenetic landscape, influencing processes like cell differentiation, proliferation, and stress responses (Reid et al., 2017, Trends in Cell Biology). In many diseases, particularly cancer, this crosstalk is hijacked; for example, mutations in metabolic enzymes like isocitrate dehydrogenase (IDH) produce oncometabolites like 2-hydroxyglutarate that competitively inhibit epigenetic erasers, leading to hypermethylation and oncogenic transformation (Dang et al., 2009, Nature). Therapeutic interventions targeting this axis include inhibitors of mutant metabolic enzymes or drugs that modulate epigenetic modifiers to restore normal cellular programming (NIH, National Cancer Institute). Understanding this integration is vital for developing precision medicines that can reprogram the cellular landscape and overcome drug resistance (UniProt).

Other names

Metabolic-epigenetic axisEpigenetic-metabolic crosstalkOncometabolismMetabolic regulation of epigenetics

Inhibition of metabolic enzymes to prevent the accumulation of oncometabolites that interfere with epigenetic modifiers, or direct modulation of epigenetic enzymes that require metabolic intermediates as cofactors.