One Carbon Metabolism (Pan troglodytes)

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GlycineDNA 5-methylcytosineDeoxyuridine monophosphateThymidylate Synthesis and DNA repairDeoxythymidine monophosphateSerine5-Formimino TetrahydrafolateAlcoholvitamin B6Methyl-cobalaminDNACobalamin5-Formyl Tetrahydrafolatevitamin B2MTHFD1LMTHFD1MTHFD1LHomocysteineS-adenosylhomocysteineMethionineFTCDMTHFD1LFOLH1MTHFD1DHFRAHCYL25-Methyl TetrahydrofolateMTHFD2MTHFD2MTHFRDNMT3ATCN2AMTMAT2BMTHFD1BetaineDNMT3BMTRRALDH1L1MTRATICGARTAHCYDHFRMTFMTDHFRTetrahydrofolateDNMT1TYMSMAT1A5,10-Methenyl TetrahydrofolateMonoglutamateSHMT2S-AdenosylmethionineGARTSHMT1FTCDMTHFSAMT10-Formyl TetrahydrofolateBHMTPolyglutamateDihydrofolate5,10-Methylene Tetrahydrofolate1111111111111111111111111111


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 100% conversion rate.

Quality Tags

Ontology Terms

 

Bibliography

  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

History

View all...
CompareRevisionActionTimeUserComment
89676view08:18, 24 September 2016EgonwReplaced the CAS for polyglutamate with the ChEBI ID for this metabolite.
88016view13:29, 25 July 2016ElisaOntology Term : 'classic metabolic pathway' added !
69286view18:40, 8 July 2013MaintBotUpdated to 2013 gpml schema
41595view02:01, 2 March 2011MaintBotRemoved redundant pathway information and comments
33567view09:45, 1 December 2009MaintBotRemoved group label
30478view21:34, 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 TetrahydrofolateMetabolite12071 (ChEBI)
5-Methyl TetrahydrofolateMetabolite134-35-0 (CAS)
AHCYGeneProduct458190 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
AHCYL2GeneProduct463719 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
ALDH1L1GeneProduct460655 (Entrez Gene)
AMTGeneProduct461012 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
ATICGeneProduct459925 (Entrez Gene)
BHMTGeneProduct461786 (Entrez Gene)
BetaineMetabolite107-43-7 (CAS)
DHFRGeneProduct735442 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
DNMT1GeneProduct455696 (Entrez Gene)
DNMT3AGeneProduct739139 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
DNMT3BGeneProduct458174 (Entrez Gene) KEGG database: Methionine metabolism - Homo sapiens (human)
DihydrofolateMetabolite4033-27-6 (CAS)
FOLH1GeneProduct451185 (Entrez Gene)
FTCDGeneProduct474057 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
GARTGeneProduct458518 (Entrez Gene)
HomocysteineMetabolite6027-13-0 (CAS)
MAT1AGeneProduct450555 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
MAT2BGeneProduct462245 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
MTFMTGeneProduct453511 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
MTHFD1GeneProduct452965 (Entrez Gene)
MTHFD1LGeneProduct463073 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
MTHFD2GeneProduct459331 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
MTHFRGeneProduct469800 (Entrez Gene)
MTHFSGeneProduct453578 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
MTRGeneProduct457844 (Entrez Gene)
MTRRGeneProduct461717 (Entrez Gene)
MethionineMetabolite63-68-3 (CAS)
MonoglutamateMetabolite59-30-3 (CAS)
PolyglutamateMetabolite25513-46-6 (CAS)
S-AdenosylmethionineMetabolite29908-03-0 (CAS)
S-adenosylhomocysteineMetabolite979-92-0 (CAS)
SHMT1GeneProduct454490 (Entrez Gene)
SHMT2GeneProduct452007 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
TCN2GeneProduct470178 (Entrez Gene)
TYMSGeneProduct740018 (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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