One-carbon metabolism (WP241)

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. The pathway is also illustrative of the role of a number of B vitamins, including vitamin B12 (cobalamine) which is important for the sythesis of folate (vitamin B9) and of methionine. Proteins on this pathway have targeted assays available via the [ CPTAC Assay Portal]
last edited


Michiel, Frank, Thomas, MaintBot, Txr24, Egoyenechea, Evelo, AlexanderPico, Khanspers, Egonw, Iamlove, MirellaKalafati, Garima.thakur, DeSl, Fehrhart, and Eweitz

Cited In


Homo sapiens


CPTAC Micronutrients


Pathway Ontology: folate mediated one-carbon metabolic pathway


Label Type Compact Identifier
Deoxyuridine monophosphate Metabolite pubchem.compound:65063
Deoxythymidine monophosphate Metabolite pubchem.compound:9700
MAT1A GeneProduct ncbigene:4143
BHMT GeneProduct ncbigene:635
Tetrahydrofolate Metabolite cas:135-16-0
5-Methyl Tetrahydrofolate Metabolite cas:134-35-0
GRX1 GeneProduct ncbigene:2745
MTHFS GeneProduct ncbigene:10588
DHFR GeneProduct ncbigene:1719
MTHFD2 GeneProduct ncbigene:10797
MTHFD1 GeneProduct ncbigene:4522
MTHFD1L GeneProduct ncbigene:25902
Alcohol Metabolite pubchem.compound:702
FOLH1 GeneProduct ncbigene:2346
Betaine Metabolite cas:107-43-7
glycine Metabolite hmdb:HMDB0000123
MTFMT GeneProduct ncbigene:123263
DNMT1 GeneProduct ncbigene:1786
MTHFD1 GeneProduct ncbigene:4522
Thymidylate Synthesis Pathway wikipathways:WP4225
CHDH GeneProduct uniprot:Q8NE62
5-Formyl Tetrahydrofolate Metabolite cas:135-16-0
Zn Metabolite hmdb:HMDB0015532
RiboflavinVitamin B2 Metabolite hmdb:HMDB0000244
10-Formyl Tetrahydrofolate Metabolite cas:2800-34-2
MTR GeneProduct ncbigene:4548
5,10-Methenyl Tetrahydrofolate Metabolite cas:7444-29-3
MTHFR GeneProduct ncbigene:4524
MTHFD1L GeneProduct ncbigene:25902
FTCD GeneProduct ncbigene:10841
Choline Metabolite cas:62-49-7
5-Formimino Tetrahydrofolate Metabolite cas:135-16-0
DNMT3b GeneProduct ncbigene:1789
Non-homologous end joining Pathway wikipathways:WP438
KIAA0828 GeneProduct ncbigene:23382
ALDH1L1 GeneProduct ncbigene:10840
AMT GeneProduct ncbigene:275
MTRR GeneProduct ncbigene:4552
Folate Metabolite cas:59-30-3
DihydrofolateVitamin B9 Metabolite cas:4033-27-6
MAT2B GeneProduct ncbigene:27430
5,10-Methylene Tetrahydrofolate Metabolite chebi:12071
Methionine Metabolite cas:63-68-3
FTCD GeneProduct ncbigene:10841
SHMT1 GeneProduct ncbigene:6470
AMT GeneProduct ncbigene:275
MIsmatch repair Pathway wikipathways:WP531
S-adenosylhomocysteine Metabolite cas:979-92-0
S-Adenosylmethionine Metabolite cas:29908-03-0
TYMS GeneProduct ncbigene:7298
MTHFD1 GeneProduct ncbigene:4522
Cobalamin Metabolite hmdb:HMDB0002174
serine Metabolite pubchem.compound:617
MethylcobalaminB12 Metabolite hmdb:HMDB0002274
GART GeneProduct ncbigene:2618
SHMT2 GeneProduct ncbigene:6472
MTHFD1L GeneProduct ncbigene:25902
DNMT3a GeneProduct ncbigene:1788
Homocystine Metabolite chebi:17485
Pyridoxal 5-phosphateVitamin B6 Metabolite HMDB
ATIC GeneProduct Entrez Gene
Homocysteine Metabolite HMDB
MTHFD2 GeneProduct Entrez Gene
AHCY GeneProduct Entrez Gene
TCN II GeneProduct Entrez Gene
GART GeneProduct Entrez Gene
DHFR GeneProduct Entrez Gene
DHFR GeneProduct Entrez Gene
Polyglutamate Metabolite CAS


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