One Carbon Metabolism (Anopheles gambiae)

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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 51% 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

History

View all...
CompareRevisionActionTimeUserComment
88010view13:29, 25 July 2016ElisaOntology Term : 'classic metabolic pathway' added !
77346view15:19, 24 August 2014EgonwFixed the Chemspider data sources.
77345view15:09, 24 August 2014EgonwConverted three labels into metabolite DataNodes with an identifier.
68447view19:21, 5 July 2013MaintBotUpdated to 2013 gpml schema
40480view18:47, 1 March 2011MaintBotRemoved redundant pathway information and comments
31837view12:28, 14 August 2009MaintBotFixed group labels
30799view23:45, 29 July 2009MaintBotNew pathway

External references

Datanodes

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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)
ALDH1L1GeneProduct
AgaP_AGAP000398GeneProduct1271848 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
AgaP_AGAP000719GeneProduct1272312 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
AgaP_AGAP000792GeneProduct1272386 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
AgaP_AGAP001065GeneProduct1278659 (Entrez Gene)
AgaP_AGAP001124GeneProduct1282039 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
AgaP_AGAP001423GeneProduct1281753 (Entrez Gene)
AgaP_AGAP002830GeneProduct1273131 (Entrez Gene)
AgaP_AGAP004677GeneProduct1275382 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
AgaP_AGAP006824GeneProduct1270240 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
AgaP_AGAP009786GeneProduct1279199 (Entrez Gene)
AgaP_AGAP010278GeneProduct1279701 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
AgaP_AGAP010457GeneProduct1272582 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
BHMTGeneProduct
BetaineMetabolite107-43-7 (CAS)
DNMT1GeneProduct
DNMT3aGeneProductKEGG Database Methionine metabolism - Homo sapiens (human)
DNMT3bGeneProductKEGG database: Methionine metabolism - Homo sapiens (human)
Deoxythymidine monophosphateMetabolite315142 (Chemspider)
DihydrofolateMetabolite4033-27-6 (CAS)
FOLH1GeneProduct
FTCDGeneProductKEGG database: One carbon pool by folate - Homo sapiens (human)
GlycineMetabolite730 (Chemspider)
HomocysteineMetabolite6027-13-0 (CAS)
MAT1AGeneProductKEGG Database Methionine metabolism - Homo sapiens (human)
MAT2BGeneProductKEGG Database Methionine metabolism - Homo sapiens (human)
MTHFD1LGeneProductKEGG database: One carbon pool by folate - Homo sapiens (human)
MTHFRGeneProduct
MTRGeneProduct
MTRRGeneProduct
MethionineMetabolite63-68-3 (CAS)
MonoglutamateMetabolite59-30-3 (CAS)
PolyglutamateMetabolite25513-46-6 (CAS)
S-AdenosylmethionineMetabolite29908-03-0 (CAS)
S-adenosylhomocysteineMetabolite979-92-0 (CAS)
SHMT2GeneProductKEGG database: One carbon pool by folate - Homo sapiens (human)
SerineMetabolite597 (Chemspider)
TCN IIGeneProduct
TetrahydrofolateMetabolite135-16-0 (CAS)

Annotated Interactions

No annotated interactions
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