Folic Acid Network (Rattus norvegicus)

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1861791513, 221620242, 27282611, 231921314BBSynthesis of cholineMETABOLITEBReactionINTRACELULARCNBBConversionFormation of methionineBindingBCompetitionBUnspecified interactionINORGANIC IONBTInterconversionTMain functionsPLASMABBBBPositive effectTransformationTFormation of HemeBBBBBBBUnspecified effectTransportBBBTBNegative effectTBInfluence on expressionBTTTTBIENucleotide biosynthesisGeneric enzymeBBPGH3Zinc15-HETELipoxin A4Txnrd2SeleniumManganeseLeukotriene D4Fads2iPF2-alphaEPA (n-3)COX1BPtges5,10-METHYL-THFLeukotrieneE4Sod1Methionine sulfoxide5-HPETEPGG2CobalaminTromboxane A2NiacinEPA (n-3)SerineS-Adenosylhomocysteine Txnrd1PGH2Ascorbic acidALA (n-3)a TocopherolHypoxanthinePGE21-methylnicotinamideCNAdipic acid IEPGI2TryptophanMethylmalonic acidUric acidGpx4TFOLIC ACIDHomocysteineSeleniumS-Adenosylmethionine HomocysteineCalciumL-Glutamic acidLeukotriene B4BNADPHCbsGpx15,10-METHYL-THFGlutathione disulfideTRXR 3d5 desaturaseLeukotriene F415-HETEMthfrPGG3Gpx6KmoPGE2TranscobalaminPGD2ALA (n-3)2-Ketobutyric acidIronHemeROSF2-IsoprostaneGpx3Leukotriene A4Glutathioned4 desaturaseXdhZincLeukotriene B4Pyridoxal-5'-phosphateNADPHCopperPyridoxal-5'-phosphatePtgisNADPUric acidO2EthanolamineSepw1CobalaminMethylmalonic acid EthanolamineS-Adenosylhomocysteine TTC22:5 (n-6)Alox5NADPThioredoxinThromboxane B2AA (n-6)1-MethylnicotinamideSepx1IronAA (n-6)S-AdenosylmethionineCopperDHA (n-3)L-Glutamic acidGlycine2-Ketobutyric acidCysteineLA (n-6)PGF2aLipoxin A4EndoperoxidaseRiboflavinCOX2LA (n-6)MtrPGFSLeukotriene C4DHA (n-3)PtgdsPGF2aCalciumL-MethionineCarnitineFADLeukotrieneE4Gpx2HypoxanthineLeukotriene C4Lipoxin B4Ascorbic acidLeukotriene D4FMN1CholineNicotinamideGsrSerineGlycineC22:5 (n-6)CystathioneVitamin B12THASSelkPGD2Adipic acidThromboxane A2Lipoic acidFOLIC ACIDCysteinePNPOa-tocopherolGlutathionePGI2PGE3H2O2Vitamin B12MethionineH2OXanthineBetaineCat815, 2529710412


The folic acid-centred micronutrient biological network. The most relevant biochemical processes related to folic acid in the context of metabolism, oxidation and inflammation are represented. Also, the compartmental separation (intracellular vs. plasma) is presented, identifying the folic acid centred plasma metabolome.


This pathway was inferred from Homo sapiens pathway WP176(r30153) with a 58% conversion rate.

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Ontology Terms



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  1. George J, Struthers AD.; ''The role of urate and xanthine oxidase inhibitors in cardiovascular disease.''; Cardiovasc Ther., 2008 PubMed Europe PMC
  2. Hall CA; ''Transcobalamins I and II as natural transport proteins of vitamin B12. ''; The Journal of clinical investigation , 1975 PubMed Europe PMC
  3. Singh U, Devaraj S, Jialal I.; ''Vitamin E, oxidative stress, and inflammation.''; Annu Rev Nutr., 2005 PubMed Europe PMC
  4. ''Food and Nutrition Board, Institute of Medicine. Vitamin B6. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Vitamin B12, Pantothenic Acid, Biotin, and Choline.''; Washington D.C.: National Academies Press, 1998
  5.; ''Folic acid''; Linus Pauling Institute
  6. Selhub J.; ''Homocysteine metabolism.''; Annu Rev Nutr, 1999 PubMed Europe PMC
  7. Denis D, Charleson S, Rackham A, Jones TR, Ford-Hutchinson AW, Lord A, Cirino M, Girard Y, Larue M, Rokach J.; ''Synthesis and biological activities of leukotriene F4 and leukotriene F4 sulfone''; Prostaglandins., 1982 PubMed Europe PMC
  8. Basu S.; ''Isoprostanes: novel bioactive products of lipid peroxidation.''; Free Radic Res., 2004 PubMed Europe PMC
  9. Morrow JD, Roberts LJ 2nd.; ''The isoprostanes. Current knowledge and directions for future research.''; Biochem Pharmacol., 1996 PubMed Europe PMC
  10. Leclerc D, Campeau E, Goyette P, Adjalla CE, Christensen B, Ross M, Eydoux P, Rosenblatt DS, Rozen R, Gravel RA.; ''Human methionine synthase: cDNA cloning and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders. ''; Hum Mol Genet. , 1996 PubMed Europe PMC
  11.; ''Arachidonic Acid Metabolism''; Ingenuity sofware
  12. Wilson A, Platt R, Wu Q, Leclerc D, Christensen B, Yang H, Gravel RA, Rozen R; ''A common variant in methionine synthase reductase combined with low cobalamin (vitamin B12) increases risk for spina bifida. ''; Molecular genetics and metabolism, 1999 PubMed Europe PMC
  13. Vladimir Kery, Loelle Poneleit, Jeffrey D. Meyer, Mark C. Manning, Jan P. Kraus; ''Binding of Pyridoxal 5'-Phosphate to the Heme Protein Human Cystathionine -Synthase''; Biochemistry. , 1998
  14. Proctor PH.; ''Free radicals, uric acid, and human disease.''; Free Radic Biol Med., 1996 PubMed Europe PMC
  15. Fowler B.; ''Homocysteine: overview of biochemistry, molecular biology, and role in disease processes. ''; Semin Vasc Med, 2005 PubMed Europe PMC
  16.; ''Prostaglandin and Leukotriene Metabolism''; Ingenuity software
  17.; ''Vitamin B 6''; Linus Paulin institute
  18. Lu C, Qiu F, Zhou H, Peng Yp, Hao W, Xu J, Yuan J, Wang S, Qiang B, Xu C, Peng X.; ''Identification and characterization of selenoprotein K: an antioxidant in cardiomyocytes.''; FEBS Lett., 2006 PubMed Europe PMC
  19. Petersen Shay K, Moreau RF, Smith EJ, Hagen TM.; ''Is alpha-lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity.''; IUBMB Life., 2008 PubMed Europe PMC
  20. Kryukov GV, Kumar RA, Koc A, Sun Z, Gladyshev VN.; ''Selenoprotein R is a zinc-containing stereo-specific methionine sulfoxide reductase.''; Proc Natl Acad Sci U S A. , 2002 PubMed Europe PMC
  21. Bandarian V, Pattridge KA, Lennon BW, Huddler DP, Matthews RG, Ludwig ML.; ''Domain alternation switches B(12)-dependent methionine synthase to the activation conformation.''; Nat Struct Biol. , 2002 PubMed Europe PMC
  22. Selhub J.; ''Homocysteine metabolism.''; Annu Rev Nutr. , 1999 PubMed Europe PMC
  23.; ''Prostaglandin and Leukotriene Metabolism''; Ingenuity software
  24. Guzik TJ, Korbut R, Adamek-Guzik T.; ''Nitric oxide and superoxide in inflammation and immune regulation.''; J Physiol Pharmacol., 2003 PubMed Europe PMC
  25. Ben van Ommen, Susan Fairweather-Tait, Andreas Freidig, Alwine Kardinaal, Augustin Scalbert, Suzan Wopereis; ''A network biology model of micronutrient related health''; Br J Nutr, 2008 PubMed Europe PMC
  26. Fernandes-Costa F: Metz J.; ''Vitamin B12 binders (transcobalamins) in serum.''; Crit Rev Clin Lab Sci. , 1982 PubMed Europe PMC
  27. Longhi RC, Fleisher LD, Tallan HH, Gaull GE.; ''Cystathionine beta-synthase deficiency: a qualitative abnormality of the deficient enzyme modified by vitamin B6 therapy.''; Pediatr Res. , 1977 PubMed Europe PMC
  28. WikiPathways; ''Selenoproteins'';


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101981view20:32, 21 November 2018EgonwRemoved whitespace in PubMed identifiers.
101975view19:53, 21 November 2018EgonwRemoved whitespace in PubMed identifiers.
85048view10:14, 10 April 2016EgonwReplaced a Wikipedia ID with a ChEBI ID.
82695view18:10, 22 October 2015EgonwFixed a typo.
74472view04:09, 25 April 2014EgonwFixed a PubMed ID.
71791view20:33, 17 October 2013MaintBotAutomated update of data sources
69407view19:00, 8 July 2013MaintBotUpdated to 2013 gpml schema
69082view18:10, 8 July 2013EgonwReplaced an outdated HMDB identifier with the 3.5 one.
68386view09:46, 4 July 2013EgonwFixed the DataNode type of two nodes with gene identifiers.
68385view09:44, 4 July 2013EgonwMade the link to Wikipedia machine readable.
67255view10:27, 26 June 2013Christine ChichesterOntology Term : 'pathway of folate cycle/metabolism' added !
60223view20:00, 14 March 2013EgonwReplaced PubChem-substance with PubChem-compound.
58959view18:31, 21 February 2013MaintBotUpdated Ensembl and UniProt data source
48281view23:34, 17 May 2012KhanspersUpdating PubChem xrefs
48270view21:58, 17 May 2012MaintBotAutomatic update of PubChem xrefs
41727view02:39, 2 March 2011MaintBotRemoved redundant pathway information and comments
34103view19:20, 9 December 2009MaintBotAutomatic update of empty xrefs
33191view18:08, 5 November 2009KhanspersModified categories
32314view13:22, 15 August 2009MaintBotFixed text labels
31908view12:49, 14 August 2009MaintBotFixed group labels
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31017view01:07, 30 July 2009MaintBotNew pathway

External references


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NameTypeDatabase referenceComment
1-MethylnicotinamideMetaboliteHMDB00699 (HMDB)
1-methylnicotinamideMetaboliteHMDB00699 (HMDB)
15-HETEMetaboliteHMDB11134 (HMDB)
2-Ketobutyric acidMetaboliteHMDB00005 (HMDB)
5,10-METHYL-THFMetaboliteHMDB01396 (HMDB)
5-HPETEMetaboliteHMDB01193 (HMDB)
AA (n-6)MetaboliteHMDB01043 (HMDB)
ALA (n-3)MetaboliteHMDB01388 (HMDB)
Adipic acid MetaboliteHMDB00448 (HMDB)
Adipic acidMetaboliteHMDB00448 (HMDB)
Alox5Protein25290 (Entrez Gene)
Ascorbic acidMetaboliteHMDB00044 (HMDB)
BetaineMetaboliteHMDB00043 (HMDB)
C22:5 (n-6)MetaboliteHMDB01976 (HMDB)
COX1Protein26195 (Entrez Gene)
COX2Protein26198 (Entrez Gene)
CalciumMetaboliteHMDB00464 (HMDB)
CarnitineMetaboliteHMDB00062 (HMDB)
CatProtein24248 (Entrez Gene)
CbsProtein24250 (Entrez Gene)
CholineMetaboliteHMDB00097 (HMDB)
CobalaminMetaboliteHMDB02174 (HMDB)
CopperMetaboliteHMDB00657 (HMDB)
CystathioneMetaboliteHMDB00099 (HMDB)
CysteineMetaboliteHMDB00574 (HMDB)
DHA (n-3)MetaboliteHMDB02183 (HMDB)
EPA (n-3)MetaboliteHMDB01999 (HMDB)
EthanolamineMetaboliteHMDB00149 (HMDB)
F2-IsoprostaneMetaboliteHMDB04659 (HMDB)
FADMetabolite703 (PubChem-compound)
FMN1GeneProduct342184 (Entrez Gene)
FOLIC ACIDMetaboliteHMDB00121 (HMDB)
Fads2Protein83512 (Entrez Gene)
Glutathione disulfideMetabolite65359 (PubChem-compound) Type your comment here
GlutathioneMetaboliteHMDB00125 (HMDB)
GlycineMetaboliteHMDB00123 (HMDB)
Gpx1Protein24404 (Entrez Gene)
Gpx2Protein29326 (Entrez Gene)
Gpx3Protein64317 (Entrez Gene)
Gpx4Protein29328 (Entrez Gene)
Gpx6Protein259233 (Entrez Gene)
GsrProteinENSRNOG00000014915 (Ensembl) Type your comment here
H2O2MetaboliteHMDB03125 (HMDB)
H2OMetaboliteHMDB02111 (HMDB)
HemeMetaboliteHMDB03178 (HMDB)
HomocysteineMetaboliteHMDB00742 (HMDB)
HypoxanthineMetaboliteHMDB00157 (HMDB)
IronMetaboliteHMDB00692 (HMDB)
KmoProtein59113 (Entrez Gene)
L-Glutamic acidMetaboliteHMDB00148 (HMDB)
L-MethionineMetaboliteHMDB00696 (HMDB)
LA (n-6)MetaboliteHMDB00673 (HMDB)
Leukotriene A4MetaboliteHMDB01337 (HMDB)
Leukotriene B4MetaboliteHMDB01085 (HMDB)
Leukotriene C4MetaboliteHMDB01198 (HMDB)
Leukotriene D4MetaboliteHMDB03080 (HMDB)
Leukotriene F4Metabolite
LeukotrieneE4MetaboliteHMDB02200 (HMDB)
Lipoic acidMetaboliteHMDB01451 (HMDB)
Lipoxin A4MetaboliteHMDB04385 (HMDB)
Lipoxin B4MetaboliteHMDB05082 (HMDB)
ManganeseMetaboliteHMDB01333 (HMDB)
Methionine sulfoxideMetaboliteHMDB02005 (HMDB)
MethionineMetaboliteHMDB00696 (HMDB)
Methylmalonic acid MetaboliteHMDB00202 (HMDB)
Methylmalonic acidMetaboliteHMDB00202 (HMDB)
MthfrProtein362657 (Entrez Gene)
MtrProtein81522 (Entrez Gene)
NADPHMetaboliteHMDB00221 (HMDB)
NADPMetaboliteHMDB00217 (HMDB)
NiacinMetaboliteHMDB01406 (HMDB)
NicotinamideMetabolite936 (PubChem-compound)
O2MetaboliteHMDB01377 (HMDB)
PGD2MetaboliteHMDB01403 (HMDB)
PGE3MetaboliteHMDB02664 (HMDB)
PGF2aMetaboliteHMDB01139 (HMDB)
PGG2MetaboliteHMDB03235 (HMDB)
PGH2MetaboliteHMDB01381 (HMDB)
PGI2MetaboliteHMDB01335 (HMDB)
PNPOProtein64533 (Entrez Gene)
PtgdsProtein25526 (Entrez Gene)
PtgesProtein59103 (Entrez Gene)
PtgisProtein25527 (Entrez Gene)
Pyridoxal-5'-phosphateMetaboliteHMDB01491 (HMDB)
ROSMetaboliteCHEBI:26523 (ChEBI)
RiboflavinMetaboliteHMDB00244 (HMDB) Type your comment here
S-Adenosylhomocysteine MetaboliteHMDB00939 (HMDB)
S-Adenosylmethionine MetaboliteHMDB01185 (HMDB)
S-AdenosylmethionineMetaboliteHMDB01185 (HMDB)
SeleniumMetaboliteHMDB01349 (HMDB)
SelkProtein290549 (Entrez Gene)
Sepw1Protein25545 (Entrez Gene)
Sepx1Protein685059 (Entrez Gene)
SerineMetaboliteHMDB00187 (HMDB)
Sod1Protein24786 (Entrez Gene)
TGeneProduct292301 (Entrez Gene)
TRXR 3Protein
ThioredoxinProtein7295 (Entrez Gene)
Thromboxane A2MetaboliteHMDB01452 (HMDB)
Thromboxane B2MetaboliteHMDB03252 (HMDB)
Tromboxane A2MetaboliteHMDB01452 (HMDB)
TryptophanMetaboliteHMDB00929 (HMDB)
Txnrd1Protein58819 (Entrez Gene)
Txnrd2Protein50551 (Entrez Gene)
Uric acidMetaboliteHMDB00289 (HMDB)
Vitamin B12MetaboliteHMDB00607 (HMDB)
XanthineMetaboliteHMDB00292 (HMDB)
XdhProtein497811 (Entrez Gene)
ZincMetaboliteHMDB01303 (HMDB)
a TocopherolMetaboliteHMDB01893 (HMDB)
a-tocopherolMetaboliteHMDB01893 (HMDB)
d4 desaturaseProtein
d5 desaturaseProtein
iPF2-alphaMetaboliteHMDB04659 (HMDB)

Annotated Interactions

No annotated interactions
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