This one-carbon metabolism pathway is centered around folate. Folate has two key carbon-carbon double bonds. Saturating one of them yields dihydrofolate (DHF) and adding an additional molecule of hydrogen across the second yields tetrahydrofolate (THF). Folates serve as donors of single carbons in any one of three oxidation states: 5-methyl-THF (CH3THF; reduced), 5,10 methylene-THF (CH2THF; intermediate) and 10-formyl-THF (CHOTHF; oxidized). The single carbon donor CH3THF is used to convert homocysteine into methionine which can then be used to methylate DNA, the donor CH2THF is used (along with a molecule of hydrogen at the site of one of the double bonds) to convert dUMP (deoxyuridylate) into dTMP (thymidylate) and the donor CHOTHF is used to set up ring closure reactions in de novo purine synthesis. CH3THF is the primary methyl-group donor for processes such as DNA methylation reactions. Purines are used both in RNA synthesis and in DNA synthesis and dTMP is synthesized srtictly for DNA synthesis, be it for DNA repair or DNA replication.
The folate pathway is central to any study related to DNA methylation, dTMP synthesis or purine synthesis.
Differential methylation (e.g. hypermethylation of tumor suppressors) as well as disturbances in nucleotide synthesis and repair, are associated with several forms of cancer. There are also indications that hypermethylation is involved in the progression of adenomas to cancer. Metabolic ProcessThis pathway was inferred from Homo sapiens pathway [http://www.wikipathways.org/index.php?title=Pathway:WP241&oldid=21183 WP241(r21183)] with a 94% conversion rate.cf5cf5cf5cf5cf5cf5cf5cf5cf5cf5cf5cf5KEGG database: One carbon pool by folate - Homo sapiens (human)KEGG database: One carbon pool by folate - Homo sapiens (human)KEGG database: One carbon pool by folate - Homo sapiens (human)KEGG Database Methionine metabolism - Homo sapiens (human)KEGG database: Methionine metabolism - Homo sapiens (human)KEGG database: One carbon pool by folate - Homo sapiens (human)KEGG database: One carbon pool by folate - Homo sapiens (human)KEGG database: One carbon pool by folate - Homo sapiens (human)KEGG database: One carbon pool by folate - Homo sapiens (human)cf5KEGG database: One carbon pool by folate - Homo sapiens (human)cf5KEGG Database Methionine metabolism - Homo sapiens (human)KEGG Database Methionine metabolism - Homo sapiens (human)KEGG Database Methionine metabolism - Homo sapiens (human)KEGG Database Methionine metabolism - Homo sapiens (human)KEGG database: One carbon pool by folate - Homo sapiens (human)cf5cf5cf5cf5cf5cf5cf5cf5cf5cf5cf5cf5cf5KEGG database: One carbon pool by folate - Homo sapiens (human)KEGG database: One carbon pool by folate - Homo sapiens (human)KEGG database: One carbon pool by folate - Homo sapiens (human)KEGG database: One carbon pool by folate - Homo sapiens (human)KEGG database: One carbon pool by folate - Homo sapiens (human)cf5KEGG database: One carbon pool by folate - Homo sapiens (human)KEGG database: One carbon pool by folate - Homo sapiens (human)folate mediated one-carbon metabolic pathwayPW:0000189Pathway Ontology17389618PubMedTwenty-four non-synonymous polymorphisms in the one-carbon metabolic pathway and riskof colorectal adenoma in the Nurses' Health Study.Carcinogenesis2007Hazra AWu KKraft PFuchs CSGiovannucci ELHunter DJ