One Carbon Metabolism (Homo sapiens)

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Deoxyuridine monophosphate Deoxythymidine monophosphate DNA 5-methylcytosine DNA DNA repair pathways Non-homologous end joining MIsmatch repair BHMT Tetrahydrofolate 5-Methyl Tetrahydrofolate GRX1 MTHFS DHFR Alcohol FOLH1 Betaine glycine Thymidylate Synthesis CHDH 5-Formyl Tetrahydrofolate Zn 10-Formyl Tetrahydrofolate MTR 5,10-Methenyl Tetrahydrofolate FTCD Choline 5-Formimino Tetrahydrofolate MTRR Folate Dihydrofolate Vitamin B9 5,10-Methylene Tetrahydrofolate Methionine FTCD AMT S-adenosylhomocysteine S-Adenosylmethionine TYMS Cobalamin serine Methylcobalamin B12 GART Homocystine Pyridoxal 5'-phosphate Vitamin B6 Homocysteine TCN II DHFR DHFR Polyglutamate AMT SHMT1 SHMT2 DNMT1 DNMT3b DNMT3a MTFMT MTHFD1L ALDH1L1 MTHFD1 ATIC GART MAT1A MAT2B MTHFD2 MTHFD1 MTHFD1L Riboflavin Vitamin B2 MTHFR MTHFD1L MTHFD1 MTHFD2 KIAA0828 AHCY Name: One Carbon Metabolism Organism: Homo sapiens


Description

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.

Quality Tags

Ontology Terms

<OntologyTags></OntologyTags>

Bibliography

  1. RACKER E; ''Glutathione-homocystine transhydrogenase.''; J Biol Chem, 1955 PubMed
  2. 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
  3. 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
  4. 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
  5. Ludwig ML, Matthews RG; ''Structure-based perspectives on B12-dependent enzymes.''; Annu Rev Biochem, 1997 PubMed
  6. 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
  7. Kim HY; ''Glutaredoxin serves as a reductant for methionine sulfoxide reductases with or without resolving cysteine.''; Acta Biochim Biophys Sin (Shanghai), 2012 PubMed
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History

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RevisionActionTimeUserComment
97559view 08:19, 24 May 2018DeSlRemoved licence number
97558view 08:18, 24 May 2018DeSlConnected lines.
97557view 08:12, 24 May 2018DeSlChanged KEGG GENE ID to Uniprot
89671view 01:13, 24 September 2016EgonwReplaced the CAS for polyglutamate with the ChEBI ID for this metabolite.
85415view 04:27, 14 May 2016EgonwMore clean up.
85414view 04:04, 14 May 2016EgonwCleaned up two multi-entity reactions.
85413view 03:20, 14 May 2016EgonwClean up and mim annotation of catalyses.
85105view 04:10, 14 April 2016Garima.thakurAddition of Homocystine
83818view 15:16, 11 December 2015AlexanderPicoMerged Emma Beswick's edits from duplicate effort
82712view 02:56, 23 October 2015EgonwCleaned up the layout a bit.
82255view 04:49, 17 September 2015MirellaKalafatiPeriodical save, work in progress
82228view 02:45, 16 September 2015MirellaKalafatiCholine conversion to betaine (by choline dehydrogenase aka CHDH)
82227view 02:36, 16 September 2015MirellaKalafatiPeriodical save, work in progress
82226view 02:06, 16 September 2015MirellaKalafatiPeriodical save, work in progress
82225view 01:55, 16 September 2015MirellaKalafatiPeriodical save, work in progress
82224view 01:35, 16 September 2015MirellaKalafatiPeriodical save, work in progress
80389view 12:29, 12 June 2015AlexanderPicoReverted to version '23:01, 27 May 2015' by AlexanderPico
80249view 01:16, 28 May 2015IamlovePeriodical save, work in progress
80244view 23:01, 27 May 2015KhanspersReverted to version '15:46, 2 April 2015' by Khanspers
80150view 11:45, 14 May 2015KhanspersAdded mir29 family targeting and associated lit ref
79667view 08:46, 2 April 2015EveloChanged "monoglutamate" label to Folate
78552view 03:30, 7 January 2015MaintBotadded missing graphIds
68025view 01:18, 29 June 2013EgonwAdded a missing metabolite identifiers.
68024view 01:08, 29 June 2013EgonwConverted two labels into Metabolite DataNodes.
65710view 06:11, 11 June 2013EgonwConverted three labels to metabolite DataNodes.
61699view 16:32, 16 April 2013MaintBotupdated data node type "Unkown" to "GeneProduct" for annotated genes
49064view 01:35, 4 July 2012Eveloimproved homocysteine annotatopn
45325view 13:12, 7 October 2011KhanspersOntology Term : 'folate mediated one-carbon metabolic pathway' added !
41078view 16:20, 1 March 2011MaintBotRemoved redundant pathway information and comments
38794view 23:48, 23 September 2010Thomaslinked to dna repair pathways
36799view 05:04, 4 May 2010EveloMTHFR Riboflavin complex
36797view 04:56, 4 May 2010EveloModified description
36795view 04:38, 4 May 2010EveloAdded MTR reference
36794view 04:29, 4 May 2010EveloModified description
36793view 04:12, 4 May 2010EveloAdded more vitamins as metabolites, multiline labels
36792view 03:28, 4 May 2010EveloAdded vitamin names to metabolite labels
36779view 02:04, 4 May 2010Eveloadded connection
36699view 05:09, 16 April 2010MichielMinor edits
36698view 05:07, 16 April 2010MichielMinor cleanup
36697view 05:03, 16 April 2010MichielAdded metabolites
36696view 05:00, 16 April 2010MichielCorrected Cobalamin
36695view 04:58, 16 April 2010MichielCorrected reactions
36689view 04:08, 15 April 2010Evelocorrected typos in metabolite names
36181view 07:36, 5 March 2010EveloPeriodical save, work in progress
35855view 10:59, 18 February 2010AlexanderPicotest
34894view 17:30, 2 February 2010AlexanderPicoModified description
32642view 07:39, 24 August 2009Eveloalignment
32010view 06:19, 14 August 2009MaintBotFixed group labels
21183view 04:30, 14 November 2008MaintBot[[Pathway:Homo sapiens:One-carbon metabolism]] moved to [[Pathway:WP241]]: Moved to stable identifier
20613view 05:44, 12 November 2008Thomasfixed duplicate literature reference

External references

DataNodes

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)
CHDHGeneProductQ8NE62 (Uniprot)
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

<cite>No annotated interactions</cite>