One-carbon metabolism (WP1292)

Rattus norvegicus

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.

Authors

Daniela Digles , Egon Willighagen , Martina Summer-Kutmon , Eric Weitz , and Susan Coort

Activity

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Organisms

Rattus norvegicus

Communities

Micronutrients

Annotations

Pathway Ontology

folate mediated one-carbon metabolic pathway

Participants

Label Type Compact URI Comment
5-Formyl Tetrahydrafolate Metabolite chebi:57457
Deoxyuridine monophosphate Metabolite chebi:17622
DNA 5-methylcytosine Metabolite chebi:27551
Serine Metabolite chemspider:597
Deoxythymidine monophosphate Metabolite chemspider:315142
vitamin B6 Metabolite chebi:27306
vitamin B2 Metabolite chebi:17015
5-Formimino Tetrahydrafolate Metabolite chebi:15639
Glycine Metabolite chemspider:730
Tetrahydrofolate Metabolite cas:135-16-0
Methyl-cobalamin Metabolite chemspider:21403073
5-Methyl Tetrahydrofolate Metabolite cas:134-35-0
Cobalamin Metabolite chemspider:24921423
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
alcohol Metabolite chebi:30879
Homocysteine Metabolite cas:6027-13-0
Polyglutamate Metabolite cas:25513-46-6
Mat1a GeneProduct ncbigene:25331 KEGG Database Methionine metabolism - Homo sapiens (human)
Bhmt GeneProduct ncbigene:81508
Mthfs GeneProduct ncbigene:300886 KEGG database: One carbon pool by folate - Homo sapiens (human)
Dhfr GeneProduct ncbigene:24312 KEGG database: One carbon pool by folate - Homo sapiens (human)
Mthfd2 GeneProduct ncbigene:680308 KEGG database: One carbon pool by folate - Homo sapiens (human)
Mthfd1 GeneProduct ncbigene:64300
Mthfd1l GeneProduct ncbigene:361472 KEGG database: One carbon pool by folate - Homo sapiens (human)
FOLH1 GeneProduct ncbigene:85309
Mtfmt GeneProduct ncbigene:315763 KEGG database: One carbon pool by folate - Homo sapiens (human)
Dnmt1 GeneProduct ncbigene:84350
Mtr GeneProduct ncbigene:81522
Mthfr GeneProduct ncbigene:362657
Ftcd GeneProduct ncbigene:89833 KEGG database: One carbon pool by folate - Homo sapiens (human)
Dnmt3b GeneProduct ncbigene:444985 KEGG database: Methionine metabolism - Homo sapiens (human)
Ahcyl2 GeneProduct ncbigene:312192 KEGG Database Methionine metabolism - Homo sapiens (human)
ALDH1L1 GeneProduct ncbigene:64392
Amt GeneProduct ncbigene:306586 KEGG database: One carbon pool by folate - Homo sapiens (human)
Mtrr GeneProduct ncbigene:290947
Mat2b GeneProduct ncbigene:689330 KEGG Database Methionine metabolism - Homo sapiens (human)
Shmt1 GeneProduct ncbigene:287379
Tyms GeneProduct ncbigene:29261 KEGG database: One carbon pool by folate - Homo sapiens (human)
Gart GeneProduct ncbigene:288259
Shmt2 GeneProduct ncbigene:299857 KEGG database: One carbon pool by folate - Homo sapiens (human)
Dnmt3a GeneProduct ncbigene:444984 KEGG Database Methionine metabolism - Homo sapiens (human)
Atic GeneProduct ncbigene:81643
Ahcy GeneProduct ncbigene:29443 KEGG Database Methionine metabolism - Homo sapiens (human)
Tcn2 GeneProduct ncbigene:64365

References

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