Folic Acid Network (Canis familiaris)

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2, 1512191751825161310, 2620417148276, 29TBReactionBBBindingBNucleotide biosynthesisInterconversionINTRACELULARBNegative effectPositive effectTTransportBUnspecified effectUnspecified interactionBBMain functionsBFormation of methionineMETABOLITETransformationBBCompetitionBBGeneric enzymeConversionIEBBTBBBBCNSynthesis of cholineTBTBBINORGANIC IONBTTPLASMABBBBFormation of HemeInfluence on expressionTTBGPX1Uric acidL-Glutamic acidALOX5GPX 3 PTGISNADPAscorbic acidCalciumVitamin B12Leukotriene C4O2PNPOPGD2KMOC22:5 (n-6)IronSEPX1Leukotriene F4THASHypoxanthineNADPThioredoxinPGI2GPX 4MTRTTAA (n-6)2-Ketobutyric acidALA (n-3)RiboflavinEPA (n-3)ALA (n-3)S-Adenosylhomocysteine GlycineC22:5 (n-6)ZincPGFSCarnitineCobalaminPGE2L-MethionineAA (n-6)Leukotriene B4Tromboxane A2PTGDSLeukotrieneE4CholineAdipic acidSOD1MTHFRTCN1GlutathioneTryptophanGPX2CobalaminCATLipoic acidCopperManganeseTRXR 3GlycineUric acid1-methylnicotinamideThromboxane A2PGE3IronZincSerineNADPHd4 desaturasePGH3PGG2CalciumGSHRa Tocopherol5,10-METHYL-THFDHA (n-3)TXNRD2PGE25-HPETEH2O2a-tocopherolPTGES15-HETESeleniumVitamin B12CBSH2OGlutathione disulfideS-AdenosylmethionineMethionine sulfoxideXanthinePyridoxal-5'-phosphateLeukotriene D4FOLIC ACIDSerinePyridoxal-5'-phosphatePGH2NiacinLA (n-6)HomocysteineBetaineFOLIC ACIDCOX2CysteineFADAscorbic acidLeukotriene D4LeukotrieneE4EndoperoxidaseGPX 61-MethylnicotinamideS-Adenosylmethionine 5,10-METHYL-THFNicotinamidePGD2NADPH2-Ketobutyric acidLipoxin A4XDHPGI2Adipic acid 15-HETEDHA (n-3)L-Glutamic acidLipoxin A4ROSEPA (n-3)HomocysteineSELKBHypoxanthineMethionineCNEthanolamineLipoxin B4Methylmalonic acidThromboxane B2d5 desaturasePGF2aCOX1Leukotriene C4TXNRD1HemeLeukotriene B4PGG3Methylmalonic acid Leukotriene A4CopperPGF2aLA (n-6)S-Adenosylhomocysteine SEPW1FMN1CysteineiPF2-alphaFADS2SeleniumF2-IsoprostaneTGlutathioneBEthanolamineCystathioneIE2411233, 2221289


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 53% conversion rate.

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Ontology Terms



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  1. 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
  2. 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
  3. Proctor PH.; ''Free radicals, uric acid, and human disease.''; Free Radic Biol Med., 1996 PubMed
  4.; ''Folic acid''; Linus Pauling Institute
  5. 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
  6. Fernandes-Costa F: Metz J.; ''Vitamin B12 binders (transcobalamins) in serum.''; Crit Rev Clin Lab Sci. , 1982 PubMed
  7.; ''Prostaglandin and Leukotriene Metabolism''; Ingenuity software
  8. Fowler B.; ''Homocysteine: overview of biochemistry, molecular biology, and role in disease processes. ''; Semin Vasc Med, 2005 PubMed
  9. ''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
  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. George J, Struthers AD.; ''The role of urate and xanthine oxidase inhibitors in cardiovascular disease.''; Cardiovasc Ther., 2008 PubMed
  12. 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
  13. 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
  14. 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
  15. Basu S.; ''Isoprostanes: novel bioactive products of lipid peroxidation.''; Free Radic Res., 2004 PubMed
  16. 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
  17. Selhub J.; ''Homocysteine metabolism.''; Annu Rev Nutr, 1999 PubMed
  18. Singh U, Devaraj S, Jialal I.; '' Vitamin E, oxidative stress, and inflammation.''; Annu Rev Nutr., 2005 PubMed
  19. 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
  20. Morrow JD, Roberts LJ 2nd.; ''The isoprostanes. Current knowledge and directions for future research.''; Biochem Pharmacol., 1996 PubMed
  21. Guzik TJ, Korbut R, Adamek-Guzik T.; ''Nitric oxide and superoxide in inflammation and immune regulation.''; J Physiol Pharmacol., 2003 PubMed
  22. 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
  23. WikiPathways; ''Selenoproteins'';
  24.; ''Vitamin B 6''; Linus Paulin institute
  25. Selhub J.; ''Homocysteine metabolism.''; Annu Rev Nutr. , 1999 PubMed
  26.; ''Prostaglandin and Leukotriene Metabolism''; Ingenuity software
  27.; ''Arachidonic Acid Metabolism''; Ingenuity sofware
  28. Hall CA; ''Transcobalamins I and II as natural transport proteins of vitamin B12. ''; The Journal of clinical investigation , 1975 PubMed


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102897view10:28, 27 January 2019EgonwReplace a PubChem SID with a CID
102080view19:35, 28 November 2018EgonwRemoved whitespace in PubMed identifiers.
87512view01:51, 25 July 2016AlexanderPicoOntology Term : 'classic metabolic pathway' added !
87511view01:50, 25 July 2016AlexanderPicoOntology Term : 'folic acid deficiency pathway' added !
82694view18:08, 22 October 2015EgonwFixed a typo.
74496view15:57, 26 April 2014EgonwFixed a PubMed ID.
74164view09:50, 2 April 2014EgonwUpdated the PubChem-substance data source.
74163view09:49, 2 April 2014EgonwUpdated the PubChem-compound data source.
74162view09:47, 2 April 2014EgonwMarked two GeneProducts as such.
74158view09:35, 2 April 2014EgonwReplaced an outdated HMDB identifier with the 3.5 one.
71452view19:16, 17 October 2013MaintBotAutomated update of data sources
68508view21:52, 5 July 2013MaintBotUpdated to 2013 gpml schema
40660view21:48, 1 March 2011MaintBotRemoved redundant pathway information and comments
33952view18:21, 9 December 2009MaintBotAutomatic update of empty xrefs
33197view18:19, 5 November 2009KhanspersModified categories
32269view13:04, 15 August 2009MaintBotFixed text labels
31802view12:19, 14 August 2009MaintBotFixed group labels
31297view20:09, 13 August 2009MaintBotFixed text labels
30761view23:12, 29 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)
ALOX5Protein477753 (Entrez Gene)
Adipic acid MetaboliteHMDB00448 (HMDB)
Adipic acidMetaboliteHMDB00448 (HMDB)
Ascorbic acidMetaboliteHMDB00044 (HMDB)
BetaineMetaboliteHMDB00043 (HMDB)
C22:5 (n-6)MetaboliteHMDB01976 (HMDB)
CATProtein403474 (Entrez Gene)
CBSProtein611071 (Entrez Gene)
COX1Protein804478 (Entrez Gene)
COX2Protein804479 (Entrez Gene)
CalciumMetaboliteHMDB00464 (HMDB)
CarnitineMetaboliteHMDB00062 (HMDB)
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)
FADS2Protein483792 (Entrez Gene)
FMN1GeneProduct342184 (Entrez Gene)
FOLIC ACIDMetaboliteHMDB00121 (HMDB)
GPX 3 Protein
GPX 4Protein
GPX 6Protein
GPX1Protein442961 (Entrez Gene)
GPX2Protein480356 (Entrez Gene)
GSHRProteinType your comment here
Glutathione disulfideMetabolite65359 (PubChem-compound) Type your comment here
GlutathioneMetaboliteHMDB00125 (HMDB)
GlycineMetaboliteHMDB00123 (HMDB)
H2O2MetaboliteHMDB03125 (HMDB)
H2OMetaboliteHMDB02111 (HMDB)
HemeMetaboliteHMDB03178 (HMDB)
HomocysteineMetaboliteHMDB00742 (HMDB)
HypoxanthineMetaboliteHMDB00157 (HMDB)
IronMetaboliteHMDB00692 (HMDB)
KMOProtein480093 (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)
MTHFRProtein478230 (Entrez Gene)
MTRProtein479190 (Entrez Gene)
ManganeseMetaboliteHMDB01333 (HMDB)
Methionine sulfoxideMetaboliteHMDB02005 (HMDB)
MethionineMetaboliteHMDB00696 (HMDB)
Methylmalonic acid MetaboliteHMDB00202 (HMDB)
Methylmalonic acidMetaboliteHMDB00202 (HMDB)
NADPHMetaboliteHMDB00221 (HMDB)
NADPMetaboliteHMDB00217 (HMDB)
NiacinMetaboliteHMDB01406 (HMDB)
NicotinamideMetabolite936 (PubChem-compound)
O2MetaboliteHMDB01377 (HMDB)
PGD2MetaboliteHMDB01403 (HMDB)
PGE3MetaboliteHMDB02664 (HMDB)
PGF2aMetaboliteHMDB01139 (HMDB)
PGG2MetaboliteHMDB03235 (HMDB)
PGH2MetaboliteHMDB01381 (HMDB)
PGI2MetaboliteHMDB01335 (HMDB)
PNPOProtein480540 (Entrez Gene)
PTGDSProtein403740 (Entrez Gene)
PTGESProtein480698 (Entrez Gene)
PTGISProtein485919 (Entrez Gene)
Pyridoxal-5'-phosphateMetaboliteHMDB01491 (HMDB)
RiboflavinMetaboliteHMDB00244 (HMDB) Type your comment here
S-Adenosylhomocysteine MetaboliteHMDB00939 (HMDB)
S-Adenosylmethionine MetaboliteHMDB01185 (HMDB)
S-AdenosylmethionineMetaboliteHMDB01185 (HMDB)
SELKProtein476586 (Entrez Gene)
SEPW1Protein612109 (Entrez Gene)
SEPX1Protein611032 (Entrez Gene)
SOD1Protein403559 (Entrez Gene)
SeleniumMetaboliteHMDB01349 (HMDB)
SerineMetaboliteHMDB00187 (HMDB)
TGeneProduct403653 (Entrez Gene)
TCN1Protein612538 (Entrez Gene)
TRXR 3Protein
TXNRD1Protein474536 (Entrez Gene)
TXNRD2Protein608155 (Entrez Gene)
ThioredoxinGeneProduct7295 (Entrez Gene)
Thromboxane A2MetaboliteHMDB01452 (HMDB)
Thromboxane B2MetaboliteHMDB03252 (HMDB)
Tromboxane A2MetaboliteHMDB01452 (HMDB)
TryptophanMetaboliteHMDB00929 (HMDB)
Uric acidMetaboliteHMDB00289 (HMDB)
Vitamin B12MetaboliteHMDB00607 (HMDB)
XDHProtein483028 (Entrez Gene)
XanthineMetaboliteHMDB00292 (HMDB)
ZincMetaboliteHMDB01303 (HMDB)
a TocopherolMetaboliteHMDB01893 (HMDB)
a-tocopherolMetaboliteHMDB01893 (HMDB)
d4 desaturaseProtein
d5 desaturaseProtein
iPF2-alphaMetaboliteHMDB04659 (HMDB)

Annotated Interactions

No annotated interactions
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