One Carbon Metabolism (Homo sapiens)

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DNA 5-methylcytosineDNA repair pathwaysDeoxythymidine monophosphateDNADeoxyuridine monophosphateDihydrofolateVitamin B9ALDH1L1SHMT1AMTMTHFD1HomocystineMethylcobalaminB12GARTMTHFD1LMTHFD2MTRRDHFRFolatePyridoxal 5'-phosphateVitamin B6Alcohol5-Formimino TetrahydrofolatePolyglutamateTetrahydrofolateBHMTMTFMTAMTMTHFD1FOLH1SHMT2Non-homologous end joiningDHFRBetaineMTHFD1LDNMT1TCN IIFTCD5-Formyl Tetrahydrofolate5-Methyl TetrahydrofolateserineThymidylate SynthesisHomocysteineCholine5,10-Methenyl TetrahydrofolateMAT1AMTHFRFTCDATICMAT2BMTRDNMT3bGARTAHCYMTHFS10-Formyl TetrahydrofolateMIsmatch repairGRX1MTHFD2MethionineglycineKIAA0828DNMT3aTYMSCHDHMTHFD1DHFRS-adenosylhomocysteineS-AdenosylmethionineRiboflavinVitamin B25,10-Methylene TetrahydrofolateMTHFD1LCobalaminZn111213, 4, 611111111, 51171111111111111111


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.

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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
  2. Waditee R, Tanaka Y, Aoki K, Hibino T, Jikuya H, Takano J, Takabe T; ''Isolation and functional characterization of N-methyltransferases that catalyze betaine synthesis from glycine in a halotolerant photosynthetic organism Aphanothece halophytica.''; J Biol Chem, 2003 PubMed
  3. Papov VV, Gravina SA, Mieyal JJ, Biemann K; ''The primary structure and properties of thioltransferase (glutaredoxin) from human red blood cells.''; Protein Sci, 1994 PubMed
  4. Kim HY; ''Glutaredoxin serves as a reductant for methionine sulfoxide reductases with or without resolving cysteine.''; Acta Biochim Biophys Sin (Shanghai), 2012 PubMed
  5. Ludwig ML, Matthews RG; ''Structure-based perspectives on B12-dependent enzymes.''; Annu Rev Biochem, 1997 PubMed
  6. RACKER E; ''Glutathione-homocystine transhydrogenase.''; J Biol Chem, 1955 PubMed
  7. Boch J, Kempf B, Schmid R, Bremer E; ''Synthesis of the osmoprotectant glycine betaine in Bacillus subtilis: characterization of the gbsAB genes.''; J Bacteriol, 1996 PubMed


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89671view08:13, 24 September 2016EgonwReplaced the CAS for polyglutamate with the ChEBI ID for this metabolite.
85415view11:27, 14 May 2016EgonwMore clean up.
85414view11:04, 14 May 2016EgonwCleaned up two multi-entity reactions.
85413view10:20, 14 May 2016EgonwClean up and mim annotation of catalyses.
85105view11:10, 14 April 2016Garima.thakurAddition of Homocystine
83818view22:16, 11 December 2015AlexanderPicoMerged Emma Beswick's edits from duplicate effort
82712view09:56, 23 October 2015EgonwCleaned up the layout a bit.
82255view11:49, 17 September 2015MirellaKalafatiPeriodical save, work in progress
82228view09:45, 16 September 2015MirellaKalafatiCholine conversion to betaine (by choline dehydrogenase aka CHDH)
82227view09:36, 16 September 2015MirellaKalafatiPeriodical save, work in progress
82226view09:06, 16 September 2015MirellaKalafatiPeriodical save, work in progress
82225view08:55, 16 September 2015MirellaKalafatiPeriodical save, work in progress
82224view08:35, 16 September 2015MirellaKalafatiPeriodical save, work in progress
80389view19:29, 12 June 2015AlexanderPicoReverted to version '23:01, 27 May 2015' by AlexanderPico
80249view08:16, 28 May 2015IamlovePeriodical save, work in progress
80244view06:01, 28 May 2015KhanspersReverted to version '15:46, 2 April 2015' by Khanspers
80150view18:45, 14 May 2015KhanspersAdded mir29 family targeting and associated lit ref
79667view15:46, 2 April 2015EveloChanged "monoglutamate" label to Folate
78552view10:30, 7 January 2015MaintBotadded missing graphIds
68025view08:18, 29 June 2013EgonwAdded a missing metabolite identifiers.
68024view08:08, 29 June 2013EgonwConverted two labels into Metabolite DataNodes.
65710view13:11, 11 June 2013EgonwConverted three labels to metabolite DataNodes.
61699view23:32, 16 April 2013MaintBotupdated data node type "Unkown" to "GeneProduct" for annotated genes
49064view08:35, 4 July 2012Eveloimproved homocysteine annotatopn
45325view20:12, 7 October 2011KhanspersOntology Term : 'folate mediated one-carbon metabolic pathway' added !
41078view23:20, 1 March 2011MaintBotRemoved redundant pathway information and comments
38794view06:48, 24 September 2010Thomaslinked to dna repair pathways
36799view12:04, 4 May 2010EveloMTHFR Riboflavin complex
36797view11:56, 4 May 2010EveloModified description
36795view11:38, 4 May 2010EveloAdded MTR reference
36794view11:29, 4 May 2010EveloModified description
36793view11:12, 4 May 2010EveloAdded more vitamins as metabolites, multiline labels
36792view10:28, 4 May 2010EveloAdded vitamin names to metabolite labels
36779view09:04, 4 May 2010Eveloadded connection
36699view12:09, 16 April 2010MichielMinor edits
36698view12:07, 16 April 2010MichielMinor cleanup
36697view12:03, 16 April 2010MichielAdded metabolites
36696view12:00, 16 April 2010MichielCorrected Cobalamin
36695view11:58, 16 April 2010MichielCorrected reactions
36689view11:08, 15 April 2010Evelocorrected typos in metabolite names
36181view14:36, 5 March 2010EveloPeriodical save, work in progress
35855view17:59, 18 February 2010AlexanderPicotest
34894view00:30, 3 February 2010AlexanderPicoModified description
32642view14:39, 24 August 2009Eveloalignment
32010view13:19, 14 August 2009MaintBotFixed group labels
21183view11:30, 14 November 2008MaintBot[[Pathway:Homo sapiens:One-carbon metabolism]] moved to [[Pathway:WP241]]: Moved to stable identifier
20613view12:44, 12 November 2008Thomasfixed duplicate literature reference
15833view13:34, 5 June 2008EgoyenecheaPeriodical save, work in progress
15301view11:31, 27 May 2008Michielanchors
15218view07:50, 26 May 2008MichielAnchor correction

External references


View all...
NameTypeDatabase referenceComment
10-Formyl TetrahydrofolateMetabolite2800-34-2 (CAS)
5,10-Methenyl TetrahydrofolateMetabolite7444-29-3 (CAS)
5,10-Methylene TetrahydrofolateMetabolite12071 (ChEBI)
5-Formimino TetrahydrofolateMetabolite135-16-0 (CAS)
5-Formyl TetrahydrofolateMetabolite135-16-0 (CAS)
5-Methyl TetrahydrofolateMetabolite134-35-0 (CAS)
AHCYGeneProduct191 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
ALDH1L1GeneProduct10840 (Entrez Gene)
AMTGeneProduct275 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
ATICGeneProduct471 (Entrez Gene)
AlcoholMetabolite702 (PubChem-compound)
BHMTGeneProduct635 (Entrez Gene)
BetaineMetabolite107-43-7 (CAS)
CHDHGeneProduct1.1.99.1 (KEGG Genes)
CholineMetabolite62-49-7 (CAS)
CobalaminMetaboliteHMDB02174 (HMDB)
DHFRGeneProduct1719 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
DNMT1GeneProduct1786 (Entrez Gene)
DNMT3aGeneProduct1788 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
DNMT3bGeneProduct1789 (Entrez Gene) KEGG database: Methionine metabolism - Homo sapiens (human)
Deoxythymidine monophosphateMetabolite9700 (PubChem-compound)
Deoxyuridine monophosphateMetabolite65063 (PubChem-compound)
Dihydrofolate Vitamin B9Metabolite4033-27-6 (CAS)
FOLH1GeneProduct2346 (Entrez Gene)
FTCDGeneProduct10841 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
FolateMetabolite59-30-3 (CAS)
GARTGeneProduct2618 (Entrez Gene)
GRX1GeneProduct2745 (Entrez Gene)
HomocysteineMetaboliteHMDB00742 (HMDB)
HomocystineMetaboliteCHEBI:17485 (ChEBI)
KIAA0828GeneProduct23382 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
MAT1AGeneProduct4143 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
MAT2BGeneProduct27430 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
MIsmatch repairPathwayWP531 (WikiPathways)
MTFMTGeneProduct123263 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
MTHFD1GeneProduct4522 (Entrez Gene)
MTHFD1LGeneProduct25902 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
MTHFD2GeneProduct10797 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
MTHFRGeneProduct4524 (Entrez Gene)
MTHFSGeneProduct10588 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
MTRGeneProduct4548 (Entrez Gene)
MTRRGeneProduct4552 (Entrez Gene)
MethionineMetabolite63-68-3 (CAS)
Methylcobalamin B12MetaboliteHMDB02274 (HMDB)
Non-homologous end joiningPathwayWP438 (WikiPathways)
PolyglutamateMetabolite25513-46-6 (CAS)
Pyridoxal 5'-phosphate Vitamin B6MetaboliteHMDB01491 (HMDB)
Riboflavin Vitamin B2MetaboliteHMDB00244 (HMDB)
S-AdenosylmethionineMetabolite29908-03-0 (CAS)
S-adenosylhomocysteineMetabolite979-92-0 (CAS)
SHMT1GeneProduct6470 (Entrez Gene)
SHMT2GeneProduct6472 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
TCN IIGeneProduct6948 (Entrez Gene)
TYMSGeneProduct7298 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
TetrahydrofolateMetabolite135-16-0 (CAS)
Thymidylate SynthesisPathway
ZnMetaboliteHMDB01303 (HMDB)
glycineMetaboliteHMDB00123 (HMDB)
serineMetabolite617 (PubChem-compound)

Annotated Interactions

No annotated interactions

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