One Carbon Metabolism (Bos taurus)

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Glycinevitamin B2Deoxyuridine monophosphateDNA 5-methylcytosineMethyl-cobalaminDeoxythymidine monophosphateAlcoholvitamin B65-Formimino TetrahydrafolateDNASerine5-Formyl TetrahydrafolateCobalaminThymidylate Synthesis and DNA repair5,10-Methylene TetrahydrofolateGARTFTCDSHMT2S-adenosylhomocysteineS-AdenosylmethionineALDH1L1TCN2AMT5,10-Methenyl TetrahydrofolateAMT10-Formyl TetrahydrofolateDHFRFTCDMTHFD1LTetrahydrofolateMonoglutamateGARTMTHFD1MTHFSMTHFD2DHFRFOLH1MethionineDihydrofolateHomocysteineMTRRAHCYL2MTFMTBetaineMTHFD2ATICBHMTMTHFD1DNMT3AMAT2BAHCYMTHFD1LMTHFD15-Methyl TetrahydrofolateMAT1ASHMT1MTHFD1LDNMT1MTRPolyglutamateTYMSDHFRMTHFRDNMT3B1111111111111111111111111111


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.

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP241(r21183) with a 91% conversion rate.

Quality Tags

Ontology Terms

 

Bibliography

  1. Ludwig ML, Matthews RG; ''Structure-based perspectives on B12-dependent enzymes.''; Annu Rev Biochem, 1997 PubMed Europe PMC Scholia
  2. RACKER E; ''Glutathione-homocystine transhydrogenase.''; J Biol Chem, 1955 PubMed Europe PMC Scholia
  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 Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
105923view11:45, 16 August 2019MaintBotHMDB identifier normalization
97538view14:32, 24 May 2018Fehrhartupdated identifier
85106view11:53, 14 April 2016Garima.thakurAddition of Homocystine
80681view15:21, 30 June 2015Mkutmonhomology conversion
63333view21:13, 9 May 2013MaintBotUpdated to 2013 gpml schema
40512view19:29, 1 March 2011MaintBotRemoved redundant pathway information and comments
33755view00:00, 9 December 2009MaintBotAutomatic update of empty xrefs
31665view11:40, 14 August 2009MaintBotFixed group labels
30595view22:14, 29 July 2009MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
10-Formyl TetrahydrofolateMetabolite2800-34-2 (CAS)
5,10-Methenyl TetrahydrofolateMetabolite7444-29-3 (CAS)
5,10-Methylene TetrahydrofolateMetabolite25513-46-6 (CAS)
5-Methyl TetrahydrofolateMetabolite134-35-0 (CAS)
AHCYGeneProduct508158 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
AHCYL2GeneProduct532836 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
ALDH1L1GeneProduct505677 (Entrez Gene)
AMTGeneProduct280719 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
ATICGeneProduct506343 (Entrez Gene)
BHMTGeneProduct497025 (Entrez Gene)
BetaineMetabolite107-43-7 (CAS)
DHFRGeneProduct508809 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
DNMT1GeneProduct281119 (Entrez Gene)
DNMT3AGeneProduct359716 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
DNMT3BGeneProduct353354 (Entrez Gene) KEGG database: Methionine metabolism - Homo sapiens (human)
DihydrofolateMetabolite4033-27-6 (CAS)
FOLH1GeneProduct505865 (Entrez Gene)
FTCDGeneProduct535816 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
GARTGeneProduct281183 (Entrez Gene)
HomocysteineMetabolite6027-13-0 (CAS)
MAT1AGeneProduct541078 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
MAT2BGeneProduct614177 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
MTFMTGeneProduct286855 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
MTHFD1GeneProduct534382 (Entrez Gene)
MTHFD1LGeneProduct534296 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
MTHFD2GeneProduct517539 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
MTHFRGeneProduct497032 (Entrez Gene)
MTHFSGeneProduct513372 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
MTRGeneProduct280869 (Entrez Gene)
MTRRGeneProduct507991 (Entrez Gene)
MethionineMetabolite63-68-3 (CAS)
MonoglutamateMetabolite59-30-3 (CAS)
PolyglutamateMetabolite25513-46-6 (CAS)
S-AdenosylmethionineMetabolite29908-03-0 (CAS)
S-adenosylhomocysteineMetabolite979-92-0 (CAS)
SHMT1GeneProduct509002 (Entrez Gene)
SHMT2GeneProduct507197 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
TCN2GeneProduct281518 (Entrez Gene)
TYMSGeneProduct507631 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
TetrahydrofolateMetabolite135-16-0 (CAS)

Annotated Interactions

No annotated interactions
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