One Carbon Metabolism (Bos taurus)

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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.

The pathway is also illustrative of the role of a number of B vitamins, including vitamin B12 (cobalamine) which is important for the sythesis of folate (vitamin B9) and of methionine.

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP241(80389) with a 97.0% 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
  2. Ludwig ML, Matthews RG; ''Structure-based perspectives on B12-dependent enzymes.''; Annu Rev Biochem, 1997 PubMed
  3. RACKER E; ''Glutathione-homocystine transhydrogenase.''; J Biol Chem, 1955 PubMed


History

View all...
CompareRevisionActionTimeUserComment
85106view11:53, 14 April 2016Garima.thakurAddition of Homocystine
80681view15:21, 30 June 2015Mkutmonhomology conversion
63333view21:13, 9 May 2013MaintBotUpdated to 2013 gpml schema
40512view19:29, 1 March 2011MaintBotRemoved redundant pathway information and comments
33755view00:00, 9 December 2009MaintBotAutomatic update of empty xrefs
31665view11:40, 14 August 2009MaintBotFixed group labels
30595view22:14, 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 TetrahydrofolateMetabolite25513-46-6 (CAS)
5-Formimino TetrahydrofolateMetabolite135-16-0 (CAS)
5-Formyl TetrahydrofolateMetabolite135-16-0 (CAS)
5-Methyl TetrahydrofolateMetabolite134-35-0 (CAS)
AHCYGeneProductENSBTAG00000018101 (Ensembl)
  • KEGG Database Methionine metabolism - Homo sapiens (human)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:191
AHCYL2GeneProductENSBTAG00000001754 (Ensembl)
  • KEGG Database Methionine metabolism - Homo sapiens (human)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:23382
ALDH1L1GeneProductENSBTAG00000014470 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10840
AMTGeneProductENSBTAG00000002321 (Ensembl)
  • KEGG database: One carbon pool by folate - Homo sapiens (human)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:275
ATICGeneProductENSBTAG00000019274 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:471
AlcoholMetabolite702 (PubChem-compound)
BHMTGeneProductENSBTAG00000002255 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:635
BetaineMetabolite107-43-7 (CAS)
Cobalamin Vitamin B12MetaboliteHMDB02174 (HMDB)
DHFRGeneProductENSBTAG00000007681 (Ensembl)
  • KEGG database: One carbon pool by folate - Homo sapiens (human)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1719
DNMT1GeneProductENSBTAG00000002736 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1786
DNMT3AGeneProductENSBTAG00000021143 (Ensembl)
  • KEGG Database Methionine metabolism - Homo sapiens (human)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1788
DNMT3BGeneProductENSBTAG00000003901 (Ensembl)
  • KEGG database: Methionine metabolism - Homo sapiens (human)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1789
Deoxythymidine monophosphateMetabolite9700 (PubChem-compound)
Deoxyuridine monophosphateMetabolite65063 (PubChem-compound)
Dihydrofolate Vitamin B9Metabolite4033-27-6 (CAS)
FOLH1GeneProductENSBTAG00000007397 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2346
FTCDGeneProductENSBTAG00000020404 (Ensembl)
  • KEGG database: One carbon pool by folate - Homo sapiens (human)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10841
FolateMetabolite59-30-3 (CAS)
GARTGeneProductENSBTAG00000009188 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2618
HomocysteineMetaboliteHMDB00742 (HMDB)
HomocystineMetaboliteCHEBI:17485 (ChEBI)
MAT1AGeneProductENSBTAG00000005963 (Ensembl)
  • KEGG Database Methionine metabolism - Homo sapiens (human)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4143
MAT2BGeneProductENSBTAG00000012350 (Ensembl)
  • KEGG Database Methionine metabolism - Homo sapiens (human)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:27430
MIsmatch repairPathwayWP531 (WikiPathways)
MTFMTGeneProductENSBTAG00000021630 (Ensembl)
  • KEGG database: One carbon pool by folate - Homo sapiens (human)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:123263
MTHFD1GeneProductENSBTAG00000009641 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4522
MTHFD1LGeneProductENSBTAG00000009846 (Ensembl)
  • KEGG database: One carbon pool by folate - Homo sapiens (human)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:25902
MTHFD2GeneProductENSBTAG00000004881 (Ensembl)
  • KEGG database: One carbon pool by folate - Homo sapiens (human)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10797
MTHFRGeneProductENSBTAG00000020698 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4524
MTHFSGeneProduct
  • KEGG database: One carbon pool by folate - Homo sapiens (human)
  • HomologyConvert: Multiple homologues found: En:ENSBTAG00000020023;En:ENSBTAG00000020023;
MTRGeneProductENSBTAG00000012251 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4548
MTRRGeneProductENSBTAG00000009401 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4552
MethionineMetabolite63-68-3 (CAS)
MethylcobalaminMetaboliteHMDB02274 (HMDB)
Non-homologous end joiningPathwayWP438 (WikiPathways)
PolyglutamateMetabolite25513-46-6 (CAS)
Pyridoxal 5'-phosphate Vitamin B6MetaboliteHMDB01491 (HMDB)
Riboflavin Vitamin B2MetaboliteHMDB00244 (HMDB)
S-AdenosylmethionineMetabolite29908-03-0 (CAS)
S-adenosylhomocysteineMetabolite979-92-0 (CAS)
SHMT1GeneProductENSBTAG00000017094 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6470
SHMT2GeneProductENSBTAG00000031500 (Ensembl)
  • KEGG database: One carbon pool by folate - Homo sapiens (human)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6472
TCN2GeneProductENSBTAG00000002770 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6948
TYMSGeneProductENSBTAG00000007003 (Ensembl)
  • KEGG database: One carbon pool by folate - Homo sapiens (human)
  • HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7298
TetrahydrofolateMetabolite135-16-0 (CAS)
Thymidylate SynthesisPathway
glutaredoxin-1 ProteinNP_001032693.1 (NCBI Protein)
glycineMetaboliteHMDB00123 (HMDB)
serineMetabolite617 (PubChem-compound)

Annotated Interactions

No annotated interactions
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