Folate metabolism (WP176)

Homo sapiens

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. Proteins on this pathway have targeted assays available via the [ CPTAC Assay Portal]


Egoyenechea , Martijn Van Iersel , Thomas Kelder , Kristina Hanspers , Jill Dunham , Damariz Rivero , Jildau Bouwman , Alex Pico , Andra Waagmeester , Egon Willighagen , Martina Summer-Kutmon , Denise Slenter , Friederike Ehrhart , Youssef Walid , Eric Weitz , and Marvin Martens


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Homo sapiens




Pathway Ontology

folate metabolic pathway


Label Type Compact URI Comment
PGE1 Metabolite hmdb:HMDB0001442 Prostaglandin E1
F2-Isoprostane Metabolite wikidata:Q33659470
8-Isoprostaglandin F2a Metabolite hmdb:HMDB0005083
PGE2 Metabolite hmdb:HMDB0001220 Prostaglandin E2
Thromboxane B2 Metabolite hmdb:HMDB0003252
Thromboxane A2 Metabolite hmdb:HMDB0001452
PGF2a Metabolite hmdb:HMDB0001139 Prostaglandin F2a
NADP+ Metabolite hmdb:HMDB0000217 Nicotinamide adenine dinucleotide phosphate-Oxidized
Cysteine Metabolite hmdb:HMDB0000574
H2O2 Metabolite hmdb:HMDB0003125 Hydrogen peroxide
5,10-Methylene-THF Metabolite hmdb:HMDB0001533 5,10-Methylenetetrahydrofolate
5,10-Methenyl-THF Metabolite hmdb:HMDB0001354 5,10-Methenyltetrahydrofolic acid
5-Formyl-THF Metabolite hmdb:HMDB0001562 5-Formyltetrahydrofolate
10-Formyl-THF Metabolite hmdb:HMDB0000972 10-formyltetrahydrofolate
GAR Metabolite hmdb:HMDB0002022 glycinamide ribonucleotide
FGAR Metabolite chebi:18272 formylglycinamide ribonucleotide
Dihydrofolate Metabolite hmdb:HMDB0001056
5-methyl-THF Metabolite hmdb:HMDB0001396 5-methyltetrahydrofolate
Predominant food folate
Folate Metabolite chebi:37445 Generic term used to denote both naturally occurring folate in foods (food folate) and the synthetic form of the vitamin (folic acid).
H2O Metabolite hmdb:HMDB0002111 Glutathione disulfide
Heme Metabolite hmdb:HMDB0003178
THF Metabolite hmdb:HMDB0001846 Tetrahydrofolic acid
NADPH Metabolite hmdb:HMDB0000221 Nicotinamide adenine dinucleotide phosphate-Reduced
Manganese Metabolite hmdb:HMDB0001333
Folic acid Metabolite hmdb:HMDB0000121 Synthetic folate
RNS Metabolite chebi:62764 reactive nitrogen species
Homocysteine Metabolite hmdb:HMDB0000742
Pyridoxal 5'-phosphate Metabolite hmdb:HMDB0001491
Pyridoxal 5'-phosphate Metabolite hmdb:HMDB0001491 Vitamin B6
Glycine Metabolite hmdb:HMDB0000123
L-Arginine Metabolite hmdb:HMDB0000517
Serine Metabolite hmdb:HMDB0000187
LDL Metabolite chebi:39026 low-density lipoprotein
HDL/APOA1 Metabolite chebi:39025 high-density lipoprotein
ApoA-I is present on the majority of HDL particles and constitutes aprox 70% of the apolipoprotein content of HDL particles
TAG Metabolite chebi:17855 Triglyceride
Cholesterol Metabolite hmdb:HMDB0000067
HDL/SAA Metabolite chebi:39025 high-density lipoprotein
SAA circulates in plasma as a constituent of high density lipoproteins (HDL).
HDL Metabolite chebi:39025 high-density lipoprotein
oxLDL Metabolite chebi:60151 oxidized low-density lipoprotein
VLDL Metabolite chebi:39027 very-low-density lipoprotein
FMN Metabolite hmdb:HMDB0001520 Flavin Mononucleotide
HDL-C Metabolite chebi:47775 high-density lipoprotein cholesterol
Cholesterol transport
VLDL-TAG Metabolite chebi:47776 very-low-density lipoprotein-triglyceride
Triglyceride transport
VLDL/APOB Metabolite chebi:39027 very-low-density lipoprotein
The VLDL is produced in the liver, contains one molecule of apoB100
O2 Metabolite hmdb:HMDB0001377
Cob(I)alamin Metabolite hmdb:HMDB0002174 Reduced cobalamin
FAD Metabolite hmdb:HMDB0001248 Flavin adenine dinucleotide
8-OHdG Metabolite hmdb:HMDB0003333 8-Hydroxy-deoxyguanosine
Cob(II)alamin Metabolite hmdb:HMDB0002174 oxidized cobalamin
ADP Metabolite hmdb:HMDB0001341 Adenosine diphosphate
Magnesium Metabolite hmdb:HMDB0000547
Chlorine Metabolite hmdb:HMDB0000492
S-nitrosohomocysteine Metabolite pubchem.compound:3035701
Cystathionine Metabolite hmdb:HMDB0000099
ATP Metabolite hmdb:HMDB0000538 Adenosine triphosphate
Zinc Metabolite hmdb:HMDB0015532
NO Metabolite hmdb:HMDB0003378 Nitric oxide
HOCl Metabolite hmdb:HMDB0001050 Hypochlorite
O3 Metabolite chebi:25812 ozone
NO2 Metabolite chebi:33101 Nitrogen dioxide
HNO2 Metabolite chebi:25567 Nitrous acid
Fibrin Metabolite wikidata:Q27205
Riboflavin Metabolite hmdb:HMDB0000244
O2 Metabolite hmdb:HMDB0002168 Superoxide
S-Adenosylmethionine Metabolite hmdb:HMDB0001185
Methionine Metabolite hmdb:HMDB0000696
S-Adenosylhomocysteine Metabolite hmdb:HMDB0000939
ONOO/ONOOH Metabolite hmdb:HMDB0002179 Peroxynitrite
Nitrotyrosine Metabolite hmdb:HMDB0001904
Tetrahydrobiopterin Metabolite hmdb:HMDB0000027 H4B
Glucose Metabolite hmdb:HMDB0000122
Fructosamine Metabolite hmdb:HMDB0002030
Iron Metabolite hmdb:HMDB0000692
NFKB1 GeneProduct ncbigene:4790 nuclear factor NF-kappa-B p50 subunit
FOLR1 GeneProduct ncbigene:2348 folate receptor 1 (adult)
RELA GeneProduct ncbigene:5970 nuclear factor of kappa light polypeptide gene enhancer in B-cells 3, p65
MCP1 GeneProduct ncbigene:6347 Monocyte Chemotactic Protein 1
p53 GeneProduct ncbigene:7157 tumor protein p53
FOLR4 GeneProduct ncbigene:390243 folate receptor 4 (delta) homolog (mouse)
FOLR3 GeneProduct ncbigene:2352 folate receptor 3 (gamma)
SLC19A1 GeneProduct ncbigene:6573 solute carrier family 19 (folate transporter), member 1
NFKB2 GeneProduct ncbigene:4791 nuclear factor of kappa light polypeptide gene enhancer in B-cells 2
FOLR2 GeneProduct ncbigene:2350 folate receptor 2 (fetal)
SLC46A1 GeneProduct ncbigene:113235 solute carrier family 46 (folate transporter), member 1
MTHFD2 Protein ncbigene:10797 EC
methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase
MSR* Protein ncbigene:4552 EC
5-methyltetrahydrofolate-homocysteine methyltransferase reductase
MAT Protein ncbigene:4143 EC
Methionine adenosyltransferase
MTHFD1* Protein ncbigene:4522 EC
methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1
MTR* Protein ncbigene:4548 EC
5-methyltetrahydrofolate-homocysteine methyltransferase
Also known as MS
AHCY Protein ncbigene:191 EC
SHMT Protein ncbigene:6472 EC
Serine hydroxymethyltransferase
DHFR Protein ncbigene:1719 EC
Dihydrofolate reductase
CBS Protein ncbigene:875 EC
MPO Protein ncbigene:4353 EC
NOS Protein uniprot:C9J5P6 Nitric oxide synthase
Catalase Protein ncbigene:847 EC
tPA Protein ncbigene:5327 EC
plasminogen activator, tissue
Factor VII Protein ncbigene:2155 EC
coagulation factor VII (serum prothrombin conversion accelerator)
PLG Protein ncbigene:5340 EC
Thrombin Protein ncbigene:2147 EC
coagulation factor II (thrombin)
PAI-1 Protein ncbigene:5054 Serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1
GPX 4 Protein ncbigene:2879 EC
Selenoprotein-glutathione peroxidase 4
SOD3 Protein ncbigene:6649 EC
superoxide dismutase 3, extracellular
RFK Protein ncbigene:55312 EC
riboflavin kinase
GPX 3 Protein ncbigene:2878 EC
Selenoprotein-glutathione peroxidase 3
CTH Protein ncbigene:1491 EC
GPX 6 Protein ncbigene:257202 EC
Selenoprotein-glutathione peroxidase 6
GPX 2 Protein ncbigene:2877 EC
Selenoprotein-glutathione peroxidase 2
GPX 1 Protein ncbigene:2876 EC
Selenoprotein-glutathione peroxidase 1
MTHFR* Protein ncbigene:4524 EC
5,10-methylenetetrahydrofolate reductase
Homozygous of (MTHFR) 677C-T variant may have enzyme activities up to 50% lower than those without the polymorphism increasing the risk of hyperhomocysteinemia
GART Protein ncbigene:2618 EC
phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, phosphoribosylaminoimidazole synthetase
MTHFS Protein ncbigene:10588 EC
5,10-methenyltetrahydrofolate synthetase (5-formyltetrahydrofolate cyclo-ligase)
SHMT Protein ncbigene:6470 EC
Serine hydroxymethyltransferase 1 (soluble)
SOD1 Protein ncbigene:6647 EC
superoxide dismutase 1, soluble
ACT Protein ncbigene:12 alpha-1-antichymotrypsin
serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 3
APOB Protein ncbigene:338 apolipoprotein B
APOA1 Protein ncbigene:335 apolipoprotein A-I
SAA1 Protein ncbigene:6288 serum amyloid A1
ABCA1 Protein ncbigene:19 ATP-binding cassette, sub-family A (ABC1), member 1
SAA4 Protein ncbigene:6291 serum amyloid A4, constitutive
SAA2 Protein ncbigene:6289 serum amyloid A2
SRB1 Protein ncbigene:949 scavenger receptor class B, member 1
SAA3 Protein ncbigene:6290 serum amyloid A3 pseudogene
APOA1-NO2Tyr Protein ncbigene:335 Nitrotyrosinated apolipoprotein A-I
LDLR Protein ncbigene:3949 low density lipoprotein receptor
SOD2 Protein ncbigene:6648 EC
superoxide dismutase 2, mitochondrial
IL1B Protein ncbigene:3553 interleukin 1, beta
IL2 Protein ncbigene:3558 interleukin 2
Fibrinogen Protein wikidata:Q381899
CRP Protein ncbigene:1401 C-reactive protein, pentraxin-related
HBB Protein ncbigene:3043 hemoglobin, beta
INSR Protein ncbigene:3643 Insulin receptor
HBA1 Protein ncbigene:3039 hemoglobin, alpha 1
Fibrin Protein wikidata:Q27205
IL10 Protein ncbigene:3458 interferon, gamma
HbA1c Protein wikidata:Q311213 Glycated hemoglobin
IL4 Protein ncbigene:3565 interleukin 4
CSF1 Protein ncbigene:1435 colony stimulating factor 1 (macrophage)
ALB Protein ncbigene:213 albumin
D-dimer Protein wikidata:Q2162109
INS Protein ncbigene:3630 Insulin
IFNg Protein ncbigene:3458 interferon, gamma
sICAM-1 Protein ncbigene:3383 soluble intercellular adhesion molecule 1
TNFa Protein ncbigene:7124 tumor necrosis factor (TNF superfamily, member 2)
IL6 Protein ncbigene:3569 interleukin 6 (interferon, beta 2)
FLAD1 Protein ncbigene:80308 EC
FAD1 flavin adenine dinucleotide synthetase homolog (S. cerevisiae)
FGA Protein ensembl:ENSG00000171560
FGB Protein ensembl:ENSG00000171564
FGG Protein ensembl:ENSG00000171557


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