One-carbon metabolism (WP1355)

Danio rerio

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.
last edited

Authors

Elisa Cirillo , Egon Willighagen , and Eric Weitz

Cited In

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Organism

Danio rerio

Communities

Annotations

Pathway Ontology: classic metabolic pathway

Participants

Label Type Compact Identifier Comment
Tetrahydrofolate Metabolite cas:135-16-0
5-Methyl Tetrahydrofolate Metabolite cas:134-35-0
Betaine Metabolite cas:107-43-7
10-Formyl Tetrahydrofolate Metabolite cas:2800-34-2
5,10-Methenyl Tetrahydrofolate Metabolite cas:7444-29-3
Monoglutamate Metabolite cas:59-30-3
Dihydrofolate Metabolite cas:4033-27-6
5,10-Methylene Tetrahydrofolate Metabolite chebi:12071
Methionine Metabolite cas:63-68-3
S-adenosylhomocysteine Metabolite cas:979-92-0
S-Adenosylmethionine Metabolite cas:29908-03-0
Homocysteine Metabolite cas:6027-13-0
Polyglutamate Metabolite cas:25513-46-6
mat1a GeneProduct ncbigene:334195 KEGG Database Methionine metabolism - Homo sapiens (human)
bhmt GeneProduct ncbigene:322228
LOC100003075 GeneProduct ncbigene:100003075 KEGG database: One carbon pool by folate - Homo sapiens (human)
dhfr GeneProduct ncbigene:81882 KEGG database: One carbon pool by folate - Homo sapiens (human)
mthfd2 GeneProduct ncbigene:100004977 KEGG database: One carbon pool by folate - Homo sapiens (human)
mthfd1 GeneProduct ncbigene:260441
si:dkey-25e12.6 GeneProduct ncbigene:569433 KEGG database: One carbon pool by folate - Homo sapiens (human)
zgc:152651 GeneProduct ncbigene:556680 KEGG database: One carbon pool by folate - Homo sapiens (human)
dnmt1 GeneProduct ncbigene:30430
mthfd1 GeneProduct ncbigene:260441
mtr GeneProduct ncbigene:378847
si:dkeyp-100a1.4 GeneProduct ncbigene:795928
si:dkey-25e12.6 GeneProduct ncbigene:569433 KEGG database: One carbon pool by folate - Homo sapiens (human)
zgc:63647 GeneProduct ncbigene:394052 KEGG database: One carbon pool by folate - Homo sapiens (human)
dnmt4 GeneProduct ncbigene:317744 KEGG database: Methionine metabolism - Homo sapiens (human)
ahcyl2 GeneProduct ncbigene:394240 KEGG Database Methionine metabolism - Homo sapiens (human)
amt GeneProduct ncbigene:450000 KEGG database: One carbon pool by folate - Homo sapiens (human)
LOC560667 GeneProduct ncbigene:560667
zgc:110308 GeneProduct ncbigene:541347 KEGG Database Methionine metabolism - Homo sapiens (human)
zgc:63647 GeneProduct ncbigene:394052 KEGG database: One carbon pool by folate - Homo sapiens (human)
shmt1 GeneProduct ncbigene:394021
amt GeneProduct ncbigene:450000 KEGG database: One carbon pool by folate - Homo sapiens (human)
tyms GeneProduct ncbigene:81540 KEGG database: One carbon pool by folate - Homo sapiens (human)
mthfd1 GeneProduct ncbigene:260441
gart GeneProduct ncbigene:58141
shmt2 GeneProduct ncbigene:100144628 KEGG database: One carbon pool by folate - Homo sapiens (human)
si:dkey-25e12.6 GeneProduct ncbigene:569433 KEGG database: One carbon pool by folate - Homo sapiens (human)
dnmt6 GeneProduct ncbigene:553189 KEGG Database Methionine metabolism - Homo sapiens (human)
atic GeneProduct ncbigene:140622
mthfd2 GeneProduct ncbigene:100004977 KEGG database: One carbon pool by folate - Homo sapiens (human)
ahcy GeneProduct ncbigene:387530 KEGG Database Methionine metabolism - Homo sapiens (human)
si:ch211-102c2.6 GeneProduct ncbigene:407646
gart GeneProduct ncbigene:58141
dhfr GeneProduct ncbigene:81882 KEGG database: One carbon pool by folate - Homo sapiens (human)
dhfr GeneProduct ncbigene:81882 KEGG database: One carbon pool by folate - Homo sapiens (human)

References

  1. Twenty-four non-synonymous polymorphisms in the one-carbon metabolic pathway and risk of colorectal adenoma in the Nursesā€™ Health Study. Hazra A, Wu K, Kraft P, Fuchs CS, Giovannucci EL, Hunter DJ. Carcinogenesis. 2007 Jul;28(7):1510ā€“9. PubMed Europe PMC Scholia