One Carbon Metabolism (Danio rerio)

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5-Formyl Tetrahydrafolatevitamin B2DNA 5-methylcytosine5-Formimino TetrahydrafolateCobalaminDeoxyuridine monophosphateDNAMethyl-cobalaminDeoxythymidine monophosphateAlcoholSerineGlycineThymidylate Synthesis and DNA repairvitamin B6amtgartatic5-Methyl Tetrahydrofolatesi:ch211-102c2.6zgc:152651dhfr5,10-Methenyl Tetrahydrofolatemthfd2mthfd1Betainemthfd2dhfrsi:dkey-25e12.6LOC100003075Dihydrofolatemat1abhmtS-Adenosylmethionineahcyl2zgc:63647si:dkey-25e12.6LOC560667zgc:110308dnmt1ahcyS-adenosylhomocysteinePolyglutamateFOLH110-Formyl Tetrahydrofolatezgc:63647shmt2dnmt4mthfd1dhfrALDH1L1mthfd1shmt15,10-Methylene Tetrahydrofolategartsi:dkey-25e12.6MethionineHomocysteinesi:dkeyp-100a1.4dnmt6MonoglutamatetymsTetrahydrofolatemtramt1111111111111111111111111111


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 94% 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
107097view14:17, 17 September 2019MaintBotChEBI identifier normalization
89675view08:17, 24 September 2016EgonwReplaced the CAS for polyglutamate with the ChEBI ID for this metabolite.
88011view13:29, 25 July 2016ElisaOntology Term : 'classic metabolic pathway' added !
68673view05:31, 6 July 2013MaintBotUpdated to 2013 gpml schema
40846view22:19, 1 March 2011MaintBotRemoved redundant pathway information and comments
31938view12:57, 14 August 2009MaintBotFixed group labels
31066view01:28, 30 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 TetrahydrofolateMetaboliteCHEBI:12071 (ChEBI)
5-Methyl TetrahydrofolateMetabolite134-35-0 (CAS)
ALDH1L1GeneProduct
BetaineMetabolite107-43-7 (CAS)
DihydrofolateMetabolite4033-27-6 (CAS)
FOLH1GeneProduct
HomocysteineMetabolite6027-13-0 (CAS)
LOC100003075GeneProduct100003075 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
LOC560667GeneProduct560667 (Entrez Gene)
MethionineMetabolite63-68-3 (CAS)
MonoglutamateMetabolite59-30-3 (CAS)
PolyglutamateMetabolite25513-46-6 (CAS)
S-AdenosylmethionineMetabolite29908-03-0 (CAS)
S-adenosylhomocysteineMetabolite979-92-0 (CAS)
TetrahydrofolateMetabolite135-16-0 (CAS)
ahcyGeneProduct387530 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
ahcyl2GeneProduct394240 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
amtGeneProduct450000 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
aticGeneProduct140622 (Entrez Gene)
bhmtGeneProduct322228 (Entrez Gene)
dhfrGeneProduct81882 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
dnmt1GeneProduct30430 (Entrez Gene)
dnmt4GeneProduct317744 (Entrez Gene) KEGG database: Methionine metabolism - Homo sapiens (human)
dnmt6GeneProduct553189 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
gartGeneProduct58141 (Entrez Gene)
mat1aGeneProduct334195 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
mthfd1GeneProduct260441 (Entrez Gene)
mthfd2GeneProduct100004977 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
mtrGeneProduct378847 (Entrez Gene)
shmt1GeneProduct394021 (Entrez Gene)
shmt2GeneProduct100144628 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
si:ch211-102c2.6GeneProduct407646 (Entrez Gene)
si:dkey-25e12.6GeneProduct569433 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
si:dkeyp-100a1.4GeneProduct795928 (Entrez Gene)
tymsGeneProduct81540 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
zgc:110308GeneProduct541347 (Entrez Gene) KEGG Database Methionine metabolism - Homo sapiens (human)
zgc:152651GeneProduct556680 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)
zgc:63647GeneProduct394052 (Entrez Gene) KEGG database: One carbon pool by folate - Homo sapiens (human)

Annotated Interactions

No annotated interactions
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