One-carbon metabolism (Rattus norvegicus)

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Thymidylate Synthesis and DNA repairDNA5-Formyl TetrahydrafolateDeoxythymidine monophosphateDNA 5-methylcytosinevitamin B2Serinevitamin B6Deoxyuridine monophosphateGlycine5-Formimino TetrahydrafolateALDH1L1Mthfd1Shmt1TymsMethyl-cobalaminMthfd2AhcyCobalaminTetrahydrofolateS-adenosylhomocysteinealcoholMthfd1lMthfd1l5,10-Methenyl TetrahydrofolateMtrrMtfmtFOLH1Dhfr10-Formyl TetrahydrofolateMthfr5-Methyl TetrahydrofolateS-AdenosylmethionineAmtShmt2MthfsDnmt3b5,10-Methylene TetrahydrofolateAticBetaineDihydrofolateGartDnmt1Tcn2Mat1aBhmtAhcyl2Mthfd1lMat2bMethionineFtcdAmtMthfd1FtcdMtrDnmt3aGartDhfrMonoglutamateDhfrPolyglutamateMthfd2Mthfd1Homocysteine1111111111111111111111111111


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.


This pathway was inferred from Homo sapiens pathway WP241(r21183) with a 94% conversion rate.

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  1. Hazra A, Wu K, Kraft P, Fuchs CS, Giovannucci EL, Hunter DJ; ''Twenty-four non-synonymous polymorphisms in the one-carbon metabolic pathway and riskof colorectal adenoma in the Nurses' Health Study.''; Carcinogenesis, 2007 PubMed Europe PMC Scholia


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116572view11:04, 8 May 2021EweitzModified title
107232view14:32, 17 September 2019MaintBotChEBI identifier normalization
89677view08:18, 24 September 2016EgonwReplaced the CAS for polyglutamate with the ChEBI ID for this metabolite.
77411view08:15, 6 September 2014EgonwConverted a few labels into metabolite DataNodes with a Chemspider and ChEBI identifiers.
71173view11:15, 11 October 2013Mkutmonfix unconnected line
70702view19:37, 28 August 2013EgonwThree more Labels into a DataNode and two ChemSpider IDs.
69394view18:58, 8 July 2013MaintBotUpdated to 2013 gpml schema
67550view11:24, 26 June 2013DdiglesOntology Term : 'folate mediated one-carbon metabolic pathway' added !
41712view02:37, 2 March 2011MaintBotRemoved redundant pathway information and comments
34091view19:16, 9 December 2009MaintBotAutomatic update of empty xrefs
31893view12:44, 14 August 2009MaintBotFixed group labels
30970view00:49, 30 July 2009MaintBotNew pathway

External references


View all...
NameTypeDatabase referenceComment
10-Formyl TetrahydrofolateMetabolite2800-34-2 (CAS)
5,10-Methenyl TetrahydrofolateMetabolite7444-29-3 (CAS)
5,10-Methylene TetrahydrofolateMetaboliteCHEBI:12071 (ChEBI)
5-Formimino TetrahydrafolateMetabolite
5-Formyl TetrahydrafolateMetaboliteCHEBI:57457 (ChEBI)
5-Methyl TetrahydrofolateMetabolite134-35-0 (CAS)
ALDH1L1GeneProduct64392 (Entrez Gene)
AhcyGeneProduct29443 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
Ahcyl2GeneProduct312192 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
AmtGeneProduct306586 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
AticGeneProduct81643 (Entrez Gene)
BetaineMetabolite107-43-7 (CAS)
BhmtGeneProduct81508 (Entrez Gene)
CobalaminMetabolite24921423 (Chemspider)
DNA 5-methylcytosineMetabolite
Deoxythymidine monophosphateMetabolite315142 (Chemspider)
Deoxyuridine monophosphateMetabolite
DhfrGeneProduct24312 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
DihydrofolateMetabolite4033-27-6 (CAS)
Dnmt1GeneProduct84350 (Entrez Gene)
Dnmt3aGeneProduct444984 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
Dnmt3bGeneProduct444985 (Entrez Gene) KEGG database: Methionine metabolism - Homo sapiens (human)
FOLH1GeneProduct85309 (Entrez Gene)
FtcdGeneProduct89833 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
GartGeneProduct288259 (Entrez Gene)
GlycineMetabolite730 (Chemspider)
HomocysteineMetabolite6027-13-0 (CAS)
Mat1aGeneProduct25331 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
Mat2bGeneProduct689330 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
MethionineMetabolite63-68-3 (CAS)
Methyl-cobalaminMetabolite21403073 (Chemspider)
MonoglutamateMetabolite59-30-3 (CAS)
MtfmtGeneProduct315763 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
Mthfd1GeneProduct64300 (Entrez Gene)
Mthfd1lGeneProduct361472 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
Mthfd2GeneProduct680308 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
MthfrGeneProduct362657 (Entrez Gene)
MthfsGeneProduct300886 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
MtrGeneProduct81522 (Entrez Gene)
MtrrGeneProduct290947 (Entrez Gene)
PolyglutamateMetabolite25513-46-6 (CAS)
S-AdenosylmethionineMetabolite29908-03-0 (CAS)
S-adenosylhomocysteineMetabolite979-92-0 (CAS)
SerineMetabolite597 (Chemspider)
Shmt1GeneProduct287379 (Entrez Gene)
Shmt2GeneProduct299857 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
Tcn2GeneProduct64365 (Entrez Gene)
TetrahydrofolateMetabolite135-16-0 (CAS)
TymsGeneProduct29261 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
vitamin B2MetaboliteCHEBI:17015 (ChEBI)
vitamin B6MetaboliteCHEBI:27306 (ChEBI)

Annotated Interactions

No annotated interactions
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