Folic Acid Network (Rattus norvegicus)

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192011, 231813, 22172, 2728326162451614921TBInfluence on expressionBINTRACELULARFormation of methionineBTTCNBReactionNegative effectBPositive effectBSynthesis of cholineTransportBTNucleotide biosynthesisIEConversionFormation of HemeMain functionsBBBindingBBINORGANIC IONMETABOLITETTransformationBTBBBBBGeneric enzymeBBBTBCompetitionTBUnspecified effectBInterconversionBBTBPLASMAUnspecified interactionBBBa-tocopherolGlutathionePtgdsTRXR 3LA (n-6)HemeCNROSF2-IsoprostaneLipoxin A4L-Glutamic acid5,10-METHYL-THFTHASFMN1O2CopperZincPGH3IronEPA (n-3)Leukotriene C4DHA (n-3)Uric acidTxnrd2C22:5 (n-6)ALA (n-3)Glutathione disulfideL-MethionineTPGH2H2O2CobalaminSelkXanthinePGE2Pyridoxal-5'-phosphateLeukotrieneE4CysteineGpx3GsrLipoic acidTranscobalaminSelenium5-HPETECOX1KmoiPF2-alphaNADPSepx1BPGD2Adipic acidCysteineTTGpx4Leukotriene D4Adipic acid XdhLeukotriene A4CystathioneTxnrd1Methylmalonic acidPGF2aCopperPGG3PGE2Lipoxin A4S-Adenosylmethionine PGF2aH2OHypoxanthineGpx2Methionine sulfoxideLeukotrieneE4HypoxanthineFOLIC ACIDTromboxane A2PtgisGpx6ThioredoxinIronAA (n-6)FOLIC ACIDEndoperoxidaseMethionine1-MethylnicotinamideFADCOX2Fads2Ascorbic acidIEMthfrMethylmalonic acid AA (n-6)Riboflavin15-HETESerinePGI2L-Glutamic acid1-methylnicotinamideSeleniumGpx15,10-METHYL-THFTryptophanGlycinePGG2PtgesSod1EthanolamineLipoxin B4PNPOLeukotriene B4PGE3NADPHDHA (n-3)MtrAscorbic acid2-Ketobutyric acidLeukotriene D4HomocysteineAlox5Pyridoxal-5'-phosphateLeukotriene C4NADPNADPHLA (n-6)Sepw1C22:5 (n-6)GlycineLeukotriene F4CobalaminVitamin B12Leukotriene B4d5 desaturaseCbsNicotinamideCalcium15-HETE2-Ketobutyric acidALA (n-3)SerinePGFSVitamin B12Thromboxane A2EPA (n-3)BetaineCatEthanolamineHomocysteineManganesea TocopherolZincPGI2GlutathioneS-Adenosylhomocysteine Thromboxane B2CarnitineUric acidNiacind4 desaturaseCholineCalciumS-AdenosylmethioninePGD2S-Adenosylhomocysteine 102941215, 2587


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
  2. Hall CA; ''Transcobalamins I and II as natural transport proteins of vitamin B12. ''; The Journal of clinical investigation , 1975 PubMed
  3. Singh U, Devaraj S, Jialal I.; ''Vitamin E, oxidative stress, and inflammation.''; Annu Rev Nutr., 2005 PubMed
  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
  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
  8. Basu S.; ''Isoprostanes: novel bioactive products of lipid peroxidation.''; Free Radic Res., 2004 PubMed
  9. Morrow JD, Roberts LJ 2nd.; ''The isoprostanes. Current knowledge and directions for future research.''; Biochem Pharmacol., 1996 PubMed
  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
  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
  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
  15. Fowler B.; ''Homocysteine: overview of biochemistry, molecular biology, and role in disease processes. ''; Semin Vasc Med, 2005 PubMed
  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
  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
  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
  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
  22. Selhub J.; ''Homocysteine metabolism.''; Annu Rev Nutr. , 1999 PubMed
  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
  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
  26. Fernandes-Costa F: Metz J.; ''Vitamin B12 binders (transcobalamins) in serum.''; Crit Rev Clin Lab Sci. , 1982 PubMed
  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
  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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