One-carbon metabolism pathway (OCM) (OCM)

One-carbon metabolism (OCM) is a fundamental metabolic network that integrates the folate and methionine cycles to facilitate the transfer of one-carbon units for essential cellular processes [1]. It is primarily responsible for the de novo synthesis of purines and thymidylate, which are required for DNA replication and repair, as well as the production of S-adenosylmethionine (SAM), the primary methyl donor for DNA, RNA, and protein methylation [2]. This pathway is highly active in rapidly proliferating cells, making it a classic target in cancer chemotherapy through the use of antifolates and antimetabolites [3]. Beyond oncology, OCM is critical for maintaining redox balance via the transsulfuration pathway and supporting amino acid metabolism [4]. Clinical manifestations of OCM dysfunction include megaloblastic anemia, neural tube defects, and elevated homocysteine levels, which are associated with increased cardiovascular risk [3, 4]. Drugs targeting this pathway, such as methotrexate, work by inhibiting key enzymes like dihydrofolate reductase, thereby depleting the pool of reduced folates necessary for nucleotide synthesis [5]. Sources: [1] Ducker, G. S., & Rabinowitz, J. D. (2017). One-Carbon Metabolism in Health and Disease. Cell Metabolism. [2] Newman, A. C., & Maddocks, O. D. (2017). One-carbon metabolism: linking growth and proliferation to cell physiology. British Journal of Cancer. [3] StatPearls. Biochemistry, One Carbon Metabolism. [4] NIH National Cancer Institute. Antimetabolites. [5] PubChem. Methotrexate.

Other names

Folate-mediated one-carbon metabolismFolate cycleMethionine cycle1C metabolism

Inhibition of specific enzymes within the folate and methionine cycles (e.g., DHFR, TS) to disrupt nucleotide synthesis and cellular methylation [3, 5].