One-carbon metabolism and glutathione synthesis pathways (OCM-GSH pathways)

One-carbon metabolism and glutathione synthesis pathways constitute a fundamental metabolic network that integrates nutrient status with critical cellular processes. One-carbon metabolism, which includes the folate and methionine cycles, provides the methyl groups necessary for DNA, RNA, and protein methylation, as well as the building blocks for purine and thymidylate synthesis (Ducker & Rabinowitz, 2017, Cell Metabolism). This system is coupled to glutathione synthesis through the transsulfuration pathway, which diverts homocysteine to produce cysteine, the rate-limiting substrate for glutathione, the cell's major antioxidant (Lu, 2013, Molecular Aspects of Medicine). In oncology, these pathways are frequently upregulated to meet the high demands of proliferating cells for nucleotides and to mitigate oxidative stress (Locasale, 2013, Nature Reviews Cancer). Therapeutic strategies targeting this network include antifolates like methotrexate and 5-fluorouracil, which disrupt DNA synthesis, and agents that modulate redox balance (Newman & Maddocks, 2017, British Journal of Cancer). Given their central role in physiology, targeting these pathways requires a balance between efficacy and the risk of systemic toxicities such as myelosuppression.

Other names

Folate-mediated one-carbon metabolismMethionine cycleTranssulfuration pathwayRedox metabolism network

Drugs typically target specific enzymes within these pathways, such as dihydrofolate reductase (DHFR) or thymidylate synthase, to inhibit DNA synthesis or modulate antioxidant capacity.