Folic Acid Network (Rattus norvegicus)

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323219284, 765, 1216241914102213, 272817Main functionsTGeneric enzymeBBBBBBBTTMETABOLITENucleotide biosynthesisTINORGANIC IONBBBBReactionInfluence on expressionUnspecified effectTransformationFormation of methionineBBBBINTRACELULARBBFormation of HemeBBTransportIEPLASMABindingInterconversionUnspecified interactionTBTBBCompetitionBNegative effectBBTSynthesis of cholineBConversionPositive effectTBBCNTS-Adenosylhomocysteine CobalaminLeukotriene F4Leukotriene C4DHA (n-3)CystathioneThromboxane B2PNPOPGD2H2O2PtgesMethylmalonic acidIronMethylmalonic acid NADPHCatS-Adenosylmethionine Thromboxane A2PGF2aSerineEthanolamineNADPFOLIC ACIDd4 desaturaseGlutathione disulfideTxnrd1Pyridoxal-5'-phosphateNiacinEndoperoxidaseGlutathioneCysteineSeleniumMtr1-MethylnicotinamideAdipic acidLeukotriene A4d5 desaturaseLA (n-6)TranscobalaminLeukotriene B4PGI2PGD2GlutathioneALA (n-3)5,10-METHYL-THFLipoxin B4CholineRiboflavinZinc2-Ketobutyric acidPyridoxal-5'-phosphateTGlycineAdipic acid ManganesePGF2aNicotinamideFads2TRXR 3EthanolamineMethioninePGE3PGFSa TocopherolAA (n-6)TTCOX2IECOX1PGH3Lipoic acidPGI215-HETESepw1GlycineEPA (n-3)HomocysteineSepx1Homocysteine1-methylnicotinamideCopperVitamin B12LA (n-6)iPF2-alphaMthfrLeukotriene D4LeukotrieneE4BetaineIronGpx2KmoLeukotrieneE4PGG2Sod1C22:5 (n-6)SerineALA (n-3)2-Ketobutyric acidXanthineH2OHypoxanthineS-AdenosylmethionineAscorbic acid15-HETEFMN1PGH2DHA (n-3)CobalaminPGG3Tromboxane A2SelkGpx4CysteineSeleniumPGE2FADCopperPtgdsF2-IsoprostaneUric acidO2Uric acid5,10-METHYL-THFVitamin B12ThioredoxinTryptophanBLipoxin A4Ba-tocopherolCalciumFOLIC ACIDZincHypoxanthinePtgisMethionine sulfoxideAlox5HemeTxnrd2NADPROSTHASXdhGsrCbsPGE2NADPHGpx1S-Adenosylhomocysteine CNLipoxin A4L-Glutamic acidEPA (n-3)Gpx3L-MethionineGpx6Leukotriene D4C22:5 (n-6)CalciumAscorbic acidCarnitine5-HPETEL-Glutamic acidLeukotriene B4AA (n-6)Leukotriene C425115, 2011182926


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. ''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
  2. Fowler B.; ''Homocysteine: overview of biochemistry, molecular biology, and role in disease processes. ''; Semin Vasc Med, 2005 PubMed Europe PMC
  3. 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
  4. Fernandes-Costa F: Metz J.; ''Vitamin B12 binders (transcobalamins) in serum.''; Crit Rev Clin Lab Sci. , 1982 PubMed Europe PMC
  5. 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
  6. 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
  7. Hall CA; ''Transcobalamins I and II as natural transport proteins of vitamin B12. ''; The Journal of clinical investigation , 1975 PubMed Europe PMC
  8.; ''Vitamin B 6''; Linus Paulin institute
  9.; ''Folic acid''; Linus Pauling Institute
  10.; ''Prostaglandin and Leukotriene Metabolism''; Ingenuity software
  11. 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
  12. 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
  13. 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
  14. 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
  15. Proctor PH.; ''Free radicals, uric acid, and human disease.''; Free Radic Biol Med., 1996 PubMed Europe PMC
  16. Basu S.; ''Isoprostanes: novel bioactive products of lipid peroxidation.''; Free Radic Res., 2004 PubMed Europe PMC
  17.; ''Prostaglandin and Leukotriene Metabolism''; Ingenuity software
  18. Morrow JD, Roberts LJ 2nd.; ''The isoprostanes. Current knowledge and directions for future research.''; Biochem Pharmacol., 1996 PubMed Europe PMC
  19. 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
  20. Guzik TJ, Korbut R, Adamek-Guzik T.; ''Nitric oxide and superoxide in inflammation and immune regulation.''; J Physiol Pharmacol., 2003 PubMed Europe PMC
  21. Selhub J.; ''Homocysteine metabolism.''; Annu Rev Nutr, 1999 PubMed Europe PMC
  22. 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
  23. Singh U, Devaraj S, Jialal I.; ''Vitamin E, oxidative stress, and inflammation.''; Annu Rev Nutr., 2005 PubMed Europe PMC
  24. George J, Struthers AD.; ''The role of urate and xanthine oxidase inhibitors in cardiovascular disease.''; Cardiovasc Ther., 2008 PubMed Europe PMC
  25.; ''Arachidonic Acid Metabolism''; Ingenuity sofware
  26. Selhub J.; ''Homocysteine metabolism.''; Annu Rev Nutr. , 1999 PubMed Europe PMC
  27. 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
  28. WikiPathways; ''Selenoproteins'';


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106963view13:42, 17 September 2019MaintBotHMDB identifier normalization
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
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31017view01:07, 30 July 2009MaintBotNew pathway

External references


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NameTypeDatabase referenceComment
1-MethylnicotinamideMetaboliteHMDB0000699 (HMDB)
1-methylnicotinamideMetaboliteHMDB0000699 (HMDB)
15-HETEMetaboliteHMDB0011134 (HMDB)
2-Ketobutyric acidMetaboliteHMDB0000005 (HMDB)
5,10-METHYL-THFMetaboliteHMDB0001396 (HMDB)
5-HPETEMetaboliteHMDB0001193 (HMDB)
AA (n-6)MetaboliteHMDB0001043 (HMDB)
ALA (n-3)MetaboliteHMDB0001388 (HMDB)
Adipic acid MetaboliteHMDB0000448 (HMDB)
Adipic acidMetaboliteHMDB0000448 (HMDB)
Alox5Protein25290 (Entrez Gene)
Ascorbic acidMetaboliteHMDB0000044 (HMDB)
BetaineMetaboliteHMDB0000043 (HMDB)
C22:5 (n-6)MetaboliteHMDB0001976 (HMDB)
COX1Protein26195 (Entrez Gene)
COX2Protein26198 (Entrez Gene)
CalciumMetaboliteHMDB0000464 (HMDB)
CarnitineMetaboliteHMDB0000062 (HMDB)
CatProtein24248 (Entrez Gene)
CbsProtein24250 (Entrez Gene)
CholineMetaboliteHMDB0000097 (HMDB)
CobalaminMetaboliteHMDB0002174 (HMDB)
CopperMetaboliteHMDB0000657 (HMDB)
CystathioneMetaboliteHMDB0000099 (HMDB)
CysteineMetaboliteHMDB0000574 (HMDB)
DHA (n-3)MetaboliteHMDB0002183 (HMDB)
EPA (n-3)MetaboliteHMDB0001999 (HMDB)
EthanolamineMetaboliteHMDB0000149 (HMDB)
F2-IsoprostaneMetaboliteHMDB0004659 (HMDB)
FADMetabolite703 (PubChem-compound)
FMN1GeneProduct342184 (Entrez Gene)
FOLIC ACIDMetaboliteHMDB0000121 (HMDB)
Fads2Protein83512 (Entrez Gene)
Glutathione disulfideMetabolite65359 (PubChem-compound) Type your comment here
GlutathioneMetaboliteHMDB0000125 (HMDB)
GlycineMetaboliteHMDB0000123 (HMDB)
Gpx1Protein24404 (Entrez Gene)
Gpx2Protein29326 (Entrez Gene)
Gpx3Protein64317 (Entrez Gene)
Gpx4Protein29328 (Entrez Gene)
Gpx6Protein259233 (Entrez Gene)
GsrProteinENSRNOG00000014915 (Ensembl) Type your comment here
H2O2MetaboliteHMDB0003125 (HMDB)
H2OMetaboliteHMDB0002111 (HMDB)
HemeMetaboliteHMDB0003178 (HMDB)
HomocysteineMetaboliteHMDB0000742 (HMDB)
HypoxanthineMetaboliteHMDB0000157 (HMDB)
IronMetaboliteHMDB0000692 (HMDB)
KmoProtein59113 (Entrez Gene)
L-Glutamic acidMetaboliteHMDB0000148 (HMDB)
L-MethionineMetaboliteHMDB0000696 (HMDB)
LA (n-6)MetaboliteHMDB0000673 (HMDB)
Leukotriene A4MetaboliteHMDB0001337 (HMDB)
Leukotriene B4MetaboliteHMDB0001085 (HMDB)
Leukotriene C4MetaboliteHMDB0001198 (HMDB)
Leukotriene D4MetaboliteHMDB0003080 (HMDB)
Leukotriene F4Metabolite
LeukotrieneE4MetaboliteHMDB0002200 (HMDB)
Lipoic acidMetaboliteHMDB0001451 (HMDB)
Lipoxin A4MetaboliteHMDB0004385 (HMDB)
Lipoxin B4MetaboliteHMDB0005082 (HMDB)
ManganeseMetaboliteHMDB0001333 (HMDB)
Methionine sulfoxideMetaboliteHMDB0002005 (HMDB)
MethionineMetaboliteHMDB0000696 (HMDB)
Methylmalonic acid MetaboliteHMDB0000202 (HMDB)
Methylmalonic acidMetaboliteHMDB0000202 (HMDB)
MthfrProtein362657 (Entrez Gene)
MtrProtein81522 (Entrez Gene)
NADPHMetaboliteHMDB0000221 (HMDB)
NADPMetaboliteHMDB0000217 (HMDB)
NiacinMetaboliteHMDB0001406 (HMDB)
NicotinamideMetabolite936 (PubChem-compound)
O2MetaboliteHMDB0001377 (HMDB)
PGD2MetaboliteHMDB0001403 (HMDB)
PGE3MetaboliteHMDB0002664 (HMDB)
PGF2aMetaboliteHMDB0001139 (HMDB)
PGG2MetaboliteHMDB0003235 (HMDB)
PGH2MetaboliteHMDB0001381 (HMDB)
PGI2MetaboliteHMDB0001335 (HMDB)
PNPOProtein64533 (Entrez Gene)
PtgdsProtein25526 (Entrez Gene)
PtgesProtein59103 (Entrez Gene)
PtgisProtein25527 (Entrez Gene)
Pyridoxal-5'-phosphateMetaboliteHMDB0001491 (HMDB)
ROSMetaboliteCHEBI:26523 (ChEBI)
RiboflavinMetaboliteHMDB0000244 (HMDB) Type your comment here
S-Adenosylhomocysteine MetaboliteHMDB0000939 (HMDB)
S-Adenosylmethionine MetaboliteHMDB0001185 (HMDB)
S-AdenosylmethionineMetaboliteHMDB0001185 (HMDB)
SeleniumMetaboliteHMDB0001349 (HMDB)
SelkProtein290549 (Entrez Gene)
Sepw1Protein25545 (Entrez Gene)
Sepx1Protein685059 (Entrez Gene)
SerineMetaboliteHMDB0000187 (HMDB)
Sod1Protein24786 (Entrez Gene)
TGeneProduct292301 (Entrez Gene)
TRXR 3Protein
ThioredoxinProtein7295 (Entrez Gene)
Thromboxane A2MetaboliteHMDB0001452 (HMDB)
Thromboxane B2MetaboliteHMDB0003252 (HMDB)
Tromboxane A2MetaboliteHMDB0001452 (HMDB)
TryptophanMetaboliteHMDB0000929 (HMDB)
Txnrd1Protein58819 (Entrez Gene)
Txnrd2Protein50551 (Entrez Gene)
Uric acidMetaboliteHMDB0000289 (HMDB)
Vitamin B12MetaboliteHMDB0000607 (HMDB)
XanthineMetaboliteHMDB0000292 (HMDB)
XdhProtein497811 (Entrez Gene)
ZincMetaboliteHMDB0001303 (HMDB)
a TocopherolMetaboliteHMDB0001893 (HMDB)
a-tocopherolMetaboliteHMDB0001893 (HMDB)
d4 desaturaseProtein
d5 desaturaseProtein
iPF2-alphaMetaboliteHMDB0004659 (HMDB)

Annotated Interactions

No annotated interactions
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