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 [https://assays.cancer.gov/available_assays?wp_id=WP176 CPTAC Assay Portal]

Authors

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

Activity

last edited

Discuss this pathway

Check for ongoing discussions or start your own.

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.

Organisms

Homo sapiens

Communities

Micronutrients

Annotations

Pathway Ontology

folate metabolic pathway

Participants

Label Type Compact URI Comment
PGE1 Metabolite hmdb:HMDB0001442 Prostaglandin E1
F2-Isoprostane Metabolite wikidata:Q33659470
F2-Isoprostane Metabolite wikidata:Q33659470
8-Isoprostaglandin F2a Metabolite hmdb:HMDB0005083
PGE1 Metabolite hmdb:HMDB0001442 Prostaglandin E1
PGE2 Metabolite hmdb:HMDB0001220 Prostaglandin E2
Thromboxane B2 Metabolite hmdb:HMDB0003252
Thromboxane A2 Metabolite hmdb:HMDB0001452
PGF2a Metabolite hmdb:HMDB0001139 Prostaglandin F2a
8-Isoprostaglandin F2a Metabolite hmdb:HMDB0005083
PGF2a Metabolite hmdb:HMDB0001139 Prostaglandin F2a
PGE2 Metabolite hmdb:HMDB0001220 Prostaglandin E2
Thromboxane B2 Metabolite hmdb:HMDB0003252
NADP+ Metabolite hmdb:HMDB0000217 Nicotinamide adenine dinucleotide phosphate-Oxidized
NADP+ Metabolite hmdb:HMDB0000217 Nicotinamide adenine dinucleotide phosphate-Oxidized
NADP+ Metabolite hmdb:HMDB0000217 Nicotinamide adenine dinucleotide phosphate-Oxidized
NADP+ Metabolite hmdb:HMDB0000217 Nicotinamide adenine dinucleotide phosphate-Oxidized
NADP+ Metabolite hmdb:HMDB0000217 Nicotinamide adenine dinucleotide phosphate-Oxidized
NADP+ Metabolite hmdb:HMDB0000217 Nicotinamide adenine dinucleotide phosphate-Oxidized
NADP+ Metabolite hmdb:HMDB0000217 Nicotinamide adenine dinucleotide phosphate-Oxidized
Cysteine Metabolite hmdb:HMDB0000574
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).
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).
5-methyl-THF Metabolite hmdb:HMDB0001396 5-methyltetrahydrofolate
Predominant food folate
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
NADPH Metabolite hmdb:HMDB0000221 Nicotinamide adenine dinucleotide phosphate-Reduced
NADPH Metabolite hmdb:HMDB0000221 Nicotinamide adenine dinucleotide phosphate-Reduced
NADPH Metabolite hmdb:HMDB0000221 Nicotinamide adenine dinucleotide phosphate-Reduced
NADPH Metabolite hmdb:HMDB0000221 Nicotinamide adenine dinucleotide phosphate-Reduced
NADPH Metabolite hmdb:HMDB0000221 Nicotinamide adenine dinucleotide phosphate-Reduced
NADPH Metabolite hmdb:HMDB0000221 Nicotinamide adenine dinucleotide phosphate-Reduced
Manganese Metabolite hmdb:HMDB0001333
Manganese Metabolite hmdb:HMDB0001333
Folic acid Metabolite hmdb:HMDB0000121 Synthetic folate
Folic acid Metabolite hmdb:HMDB0000121 Synthetic folate
RNS Metabolite chebi:62764 reactive nitrogen species
http://en.wikipedia.org/wiki/Reactive_nitrogen_species
Homocysteine Metabolite hmdb:HMDB0000742
Homocysteine Metabolite hmdb:HMDB0000742
Pyridoxal 5'-phosphate Metabolite hmdb:HMDB0001491
Pyridoxal 5'-phosphate Metabolite hmdb:HMDB0001491 Vitamin B6
Glycine Metabolite hmdb:HMDB0000123
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
LDL Metabolite chebi:39026 low-density lipoprotein
TAG Metabolite chebi:17855 Triglyceride
Triacylglycerol
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
TAG Metabolite chebi:17855 Triglyceride
Triacylglycerol
VLDL Metabolite chebi:39027 very-low-density lipoprotein
FMN Metabolite hmdb:HMDB0001520 Flavin Mononucleotide
HDL Metabolite chebi:39025 high-density lipoprotein
HDL-C Metabolite chebi:47775 high-density lipoprotein cholesterol
Cholesterol transport
HDL-C Metabolite chebi:47775 high-density lipoprotein cholesterol
Cholesterol transport
VLDL Metabolite chebi:39027 very-low-density lipoprotein
VLDL-TAG Metabolite chebi:47776 very-low-density lipoprotein-triglyceride
Triglyceride transport
oxLDL Metabolite chebi:60151 oxidized low-density lipoprotein
Cholesterol Metabolite hmdb:HMDB0000067
VLDL/APOB Metabolite chebi:39027 very-low-density lipoprotein
The VLDL is produced in the liver, contains one molecule of apoB100
VLDL-TAG Metabolite chebi:47776 very-low-density lipoprotein-triglyceride
Triglyceride transport
O2 Metabolite hmdb:HMDB0001377
Cob(I)alamin Metabolite hmdb:HMDB0002174 Reduced cobalamin
FAD Metabolite hmdb:HMDB0001248 Flavin adenine dinucleotide
Cob(I)alamin Metabolite hmdb:HMDB0002174 Reduced cobalamin
8-OHdG Metabolite hmdb:HMDB0003333 8-Hydroxy-deoxyguanosine
FAD Metabolite hmdb:HMDB0001248 Flavin adenine dinucleotide
Cob(II)alamin Metabolite hmdb:HMDB0002174 oxidized cobalamin
8-OHdG Metabolite hmdb:HMDB0003333 8-Hydroxy-deoxyguanosine
ADP Metabolite hmdb:HMDB0001341 Adenosine diphosphate
ADP Metabolite hmdb:HMDB0001341 Adenosine diphosphate
Magnesium Metabolite hmdb:HMDB0000547
Chlorine Metabolite hmdb:HMDB0000492
Chlorine Metabolite hmdb:HMDB0000492
Magnesium Metabolite hmdb:HMDB0000547
S-nitrosohomocysteine Metabolite pubchem.compound:3035701
Cystathionine Metabolite hmdb:HMDB0000099
Serine Metabolite hmdb:HMDB0000187
ATP Metabolite hmdb:HMDB0000538 Adenosine triphosphate
Zinc Metabolite hmdb:HMDB0015532
Zinc Metabolite hmdb:HMDB0015532
NO Metabolite hmdb:HMDB0003378 Nitric oxide
HOCl Metabolite hmdb:HMDB0001050 Hypochlorite
NO Metabolite hmdb:HMDB0003378 Nitric oxide
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
Methionine Metabolite hmdb:HMDB0000696
S-Adenosylmethionine Metabolite hmdb:HMDB0001185
S-Adenosylhomocysteine Metabolite hmdb:HMDB0000939
ADP Metabolite hmdb:HMDB0001341 Adenosine diphosphate
ONOO/ONOOH Metabolite hmdb:HMDB0002179 Peroxynitrite
Nitrotyrosine Metabolite hmdb:HMDB0001904
Nitrotyrosine Metabolite hmdb:HMDB0001904
Tetrahydrobiopterin Metabolite hmdb:HMDB0000027 H4B
ATP Metabolite hmdb:HMDB0000538 Adenosine triphosphate
ATP Metabolite hmdb:HMDB0000538 Adenosine triphosphate
Glucose Metabolite hmdb:HMDB0000122
Glucose Metabolite hmdb:HMDB0000122
Fructosamine Metabolite hmdb:HMDB0002030
Fructosamine Metabolite hmdb:HMDB0002030
Iron Metabolite hmdb:HMDB0000692
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
CCL2
MCP1 GeneProduct ncbigene:6347 Monocyte Chemotactic Protein 1
CCL2
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 3.5.4.9
methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase
MSR* Protein ncbigene:4552 EC 1.16.1.8
5-methyltetrahydrofolate-homocysteine methyltransferase reductase
MAT Protein ncbigene:4143 EC 2.5.1.6
Methionine adenosyltransferase
MTHFD1* Protein ncbigene:4522 EC 1.5.1.5
methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1
MTR* Protein ncbigene:4548 EC 2.1.1.13
5-methyltetrahydrofolate-homocysteine methyltransferase
Also known as MS
AHCY Protein ncbigene:191 EC 3.3.1.1
Adenosylhomocysteinase
SHMT Protein ncbigene:6472 EC 2.1.2.1
Serine hydroxymethyltransferase
DHFR Protein ncbigene:1719 EC 1.5.1.3
Dihydrofolate reductase
CBS Protein ncbigene:875 EC 4.2.1.22
cystathionine-beta-synthase
MPO Protein ncbigene:4353 EC 1.11.1.7
Myeloperoxidase
NOS Protein uniprot:C9J5P6 Nitric oxide synthase
Catalase Protein ncbigene:847 EC 1.11.1.6
MPO Protein ncbigene:4353 EC 1.11.1.7
Myeloperoxidase
tPA Protein ncbigene:5327 EC 3.4.21.68
plasminogen activator, tissue
Factor VII Protein ncbigene:2155 EC 3.4.21.21
coagulation factor VII (serum prothrombin conversion accelerator)
PLG Protein ncbigene:5340 EC 3.4.21.7
Plasminogen
tPA Protein ncbigene:5327 EC 3.4.21.68
plasminogen activator, tissue
Thrombin Protein ncbigene:2147 EC 3.4.21.5
coagulation factor II (thrombin)
Thrombin Protein ncbigene:2147 EC 3.4.21.5
coagulation factor II (thrombin)
PAI-1 Protein ncbigene:5054 Serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1
Factor VII Protein ncbigene:2155 EC 3.4.21.21
coagulation factor VII (serum prothrombin conversion accelerator)
PAI-1 Protein ncbigene:5054 Serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1
PLG Protein ncbigene:5340 EC 3.4.21.7
Plasminogen
GPX 4 Protein ncbigene:2879 EC 1.11.1.12
Selenoprotein-glutathione peroxidase 4
SOD3 Protein ncbigene:6649 EC 1.15.1.1
superoxide dismutase 3, extracellular
SOD3 Protein ncbigene:6649 EC 1.15.1.1
superoxide dismutase 3, extracellular
RFK Protein ncbigene:55312 EC 2.7.1.26
riboflavin kinase
GPX 3 Protein ncbigene:2878 EC 1.11.1.9
Selenoprotein-glutathione peroxidase 3
GPX 3 Protein ncbigene:2878 EC 1.11.1.9
Selenoprotein-glutathione peroxidase 3
CTH Protein ncbigene:1491 EC 4.4.1.1
cystathionase
GPX 6 Protein ncbigene:257202 EC 1.11.1.9
Selenoprotein-glutathione peroxidase 6
GPX 2 Protein ncbigene:2877 EC 1.11.1.9
Selenoprotein-glutathione peroxidase 2
GPX 1 Protein ncbigene:2876 EC 1.11.1.9
Selenoprotein-glutathione peroxidase 1
MTHFR* Protein ncbigene:4524 EC 1.5.1.20
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 2.1.2.2
phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, phosphoribosylaminoimidazole synthetase
MTHFS Protein ncbigene:10588 EC 6.3.3.2
5,10-methenyltetrahydrofolate synthetase (5-formyltetrahydrofolate cyclo-ligase)
SHMT Protein ncbigene:6470 EC 2.1.2.1
Serine hydroxymethyltransferase 1 (soluble)
SOD1 Protein ncbigene:6647 EC 1.15.1.1
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
APOA1 Protein ncbigene:335 apolipoprotein A-I
APOB Protein ncbigene:338 apolipoprotein B
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
ACT Protein ncbigene:12 alpha-1-antichymotrypsin
serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 3
LDLR Protein ncbigene:3949 low density lipoprotein receptor
SOD2 Protein ncbigene:6648 EC 1.15.1.1
superoxide dismutase 2, mitochondrial
IL1B Protein ncbigene:3553 interleukin 1, beta
IL2 Protein ncbigene:3558 interleukin 2
Fibrinogen Protein wikidata:Q381899
IL1B Protein ncbigene:3553 interleukin 1, beta
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
http://en.wikipedia.org/wiki/Glycated_hemoglobin
IL2 Protein ncbigene:3558 interleukin 2
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 http://en.wikipedia.org/wiki/Fibrin_degradation_product
INS Protein ncbigene:3630 Insulin
IFNg Protein ncbigene:3458 interferon, gamma
Fibrinogen Protein wikidata:Q381899
sICAM-1 Protein ncbigene:3383 soluble intercellular adhesion molecule 1
IL10 Protein ncbigene:3458 interferon, gamma
IL4 Protein ncbigene:3565 interleukin 4
IFNg Protein ncbigene:3458 interferon, gamma
TNFa Protein ncbigene:7124 tumor necrosis factor (TNF superfamily, member 2)
TNFa Protein ncbigene:7124 tumor necrosis factor (TNF superfamily, member 2)
D-dimer Protein wikidata:Q2162109 http://en.wikipedia.org/wiki/Fibrin_degradation_product
CSF1 Protein ncbigene:1435 colony stimulating factor 1 (macrophage)
IL6 Protein ncbigene:3569 interleukin 6 (interferon, beta 2)
INS Protein ncbigene:3630 Insulin
ALB Protein ncbigene:213 albumin
IL6 Protein ncbigene:3569 interleukin 6 (interferon, beta 2)
FLAD1 Protein ncbigene:80308 EC 2.7.7.2
FAD1 flavin adenine dinucleotide synthetase homolog (S. cerevisiae)
FGA Protein ensembl:ENSG00000171560
FGB Protein ensembl:ENSG00000171564
FGG Protein ensembl:ENSG00000171557

References

  1. The c-rel protooncogene product c-Rel but not NF-kappa B binds to the intronic region of the human interferon-gamma gene at a site related to an interferon-stimulable response element. Sica A, Tan TH, Rice N, Kretzschmar M, Ghosh P, Young HA. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1740–4. PubMed Europe PMC Scholia
  2. Repression of the interleukin 6 gene promoter by p53 and the retinoblastoma susceptibility gene product. Santhanam U, Ray A, Sehgal PB. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7605–9. PubMed Europe PMC Scholia
  3. Inhibition of human neutrophil superoxide generation by alpha 1-antichymotrypsin. Kilpatrick L, Johnson JL, Nickbarg EB, Wang ZM, Clifford TF, Banach M, et al. J Immunol. 1991 Apr 1;146(7):2388–93. PubMed Europe PMC Scholia
  4. Regulation of tumor necrosis factor alpha transcription in macrophages: involvement of four kappa B-like motifs and of constitutive and inducible forms of NF-kappa B. Collart MA, Baeuerle P, Vassalli P. Mol Cell Biol. 1990 Apr;10(4):1498–506. PubMed Europe PMC Scholia
  5. Kappa B-specific DNA binding proteins: role in the regulation of human interleukin-2 gene expression. Hoyos B, Ballard DW, Böhnlein E, Siekevitz M, Greene WC. Science. 1989 Apr 28;244(4903):457–60. PubMed Europe PMC Scholia
  6. Urinary 8-hydroxy-2’-deoxyguanosine as a biological marker of in vivo oxidative DNA damage. Shigenaga MK, Gimeno CJ, Ames BN. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9697–701. PubMed Europe PMC Scholia
  7. Inhibition of thromboxane formation in vivo and ex vivo: implications for therapy with platelet inhibitory drugs. Reilly IA, FitzGerald GA. Blood. 1987 Jan;69(1):180–6. PubMed Europe PMC Scholia
  8. Effects of serum amyloid A protein (SAA) on composition, size, and density of high density lipoproteins in subjects with myocardial infarction. Clifton PM, Mackinnon AM, Barter PJ. J Lipid Res. 1985 Dec;26(12):1389–98. PubMed Europe PMC Scholia
  9. Biochemistry of tryptophan in health and disease. Bender DA. Mol Aspects Med. 1983;6(2):101–97. PubMed Europe PMC Scholia
  10. Characterization of a functional NF-kappa B site in the human interleukin 1 beta promoter: evidence for a positive autoregulatory loop. Hiscott J, Marois J, Garoufalis J, D’Addario M, Roulston A, Kwan I, et al. Mol Cell Biol. 1993 Oct;13(10):6231–40. PubMed Europe PMC Scholia
  11. Repression of interleukin-2 and interleukin-4 promoters by tumor suppressor protein p53. Pesch J, Brehm U, Staib C, Grummt F. J Interferon Cytokine Res. 1996 Aug;16(8):595–600. PubMed Europe PMC Scholia
  12. Relationship of plasma folic acid and status of DNA methylation in human gastric cancer. Fang JY, Xiao SD, Zhu SS, Yuan JM, Qiu DK, Jiang SJ. J Gastroenterol. 1997 Apr;32(2):171–5. PubMed Europe PMC Scholia
  13. A molecular basis for insulin resistance. Elevated serine/threonine phosphorylation of IRS-1 and IRS-2 inhibits their binding to the juxtamembrane region of the insulin receptor and impairs their ability to undergo insulin-induced tyrosine phosphorylation. Paz K, Hemi R, LeRoith D, Karasik A, Elhanany E, Kanety H, et al. J Biol Chem. 1997 Nov 21;272(47):29911–8. PubMed Europe PMC Scholia
  14. Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuria. Leclerc D, Wilson A, Dumas R, Gafuik C, Song D, Watkins D, et al. Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3059–64. PubMed Europe PMC Scholia
  15. The metabolism of homocysteine: pathways and regulation. Finkelstein JD. Eur J Pediatr. 1998 Apr;157 Suppl 2:S40-4. PubMed Europe PMC Scholia
  16. Anxiety and adipose essential fatty acid precursors for prostaglandin E1 and E2. Mamalakis G, Kafatos A, Tornaritis M, Alevizos B. J Am Coll Nutr. 1998 Jun;17(3):239–43. PubMed Europe PMC Scholia
  17. Inflammation, antichymotrypsin, and lipid metabolism: autogenic etiology of Alzheimer’s disease. Janciauskiene S, Wright HT. Bioessays. 1998 Dec;20(12):1039–46. PubMed Europe PMC Scholia
  18. Lipid peroxidation-DNA damage by malondialdehyde. Marnett LJ. Mutat Res. 1999 Mar 8;424(1–2):83–95. PubMed Europe PMC Scholia
  19. Molecular basis for methionine synthase reductase deficiency in patients belonging to the cblE complementation group of disorders in folate/cobalamin metabolism. Wilson A, Leclerc D, Rosenblatt DS, Gravel RA. Hum Mol Genet. 1999 Oct;8(11):2009–16. PubMed Europe PMC Scholia
  20. Tissue-specific functions of individual glutathione peroxidases. Brigelius-Flohé R. Free Radic Biol Med. 1999 Nov;27(9–10):951–65. PubMed Europe PMC Scholia
  21. Relationships between homocysteine, factor VIIa, and thrombin generation in acute coronary syndromes. Al-Obaidi MK, Philippou H, Stubbs PJ, Adami A, Amersey R, Noble MM, et al. Circulation. 2000 Feb 1;101(4):372–7. PubMed Europe PMC Scholia
  22. Serine hydroxymethyltransferase and threonine aldolase: are they identical? Ogawa H, Gomi T, Fujioka M. Int J Biochem Cell Biol. 2000 Mar;32(3):289–301. PubMed Europe PMC Scholia
  23. Folate and carcinogenesis: an integrated scheme. Choi SW, Mason JB. J Nutr. 2000 Feb;130(2):129–32. PubMed Europe PMC Scholia
  24. Altered folate metabolism and disposition in mothers affected by a spina bifida pregnancy: influence of 677c --> t methylenetetrahydrofolate reductase and 2756a --> g methionine synthase genotypes. Lucock M, Daskalakis I, Briggs D, Yates Z, Levene M. Mol Genet Metab. 2000 May;70(1):27–44. PubMed Europe PMC Scholia
  25. Free radicals and hearing. Cause, consequence, and criteria. Evans P, Halliwell B. Ann N Y Acad Sci. 1999 Nov 28;884:19–40. PubMed Europe PMC Scholia
  26. Folic acid: nutritional biochemistry, molecular biology, and role in disease processes. Lucock M. Mol Genet Metab. 2000;71(1–2):121–38. PubMed Europe PMC Scholia
  27. Determination of S-adenosylmethionine and S-adenosylhomocysteine in plasma and cerebrospinal fluid by stable-isotope dilution tandem mass spectrometry. Struys EA, Jansen EE, de Meer K, Jakobs C. Clin Chem. 2000 Oct;46(10):1650–6. PubMed Europe PMC Scholia
  28. Nitric oxide is a physiological substrate for mammalian peroxidases. Abu-Soud HM, Hazen SL. J Biol Chem. 2000 Dec 1;275(48):37524–32. PubMed Europe PMC Scholia
  29. Does inflammation contribute to thrombotic events? Esmon CT. Haemostasis. 2000;30 Suppl 2:34–40. PubMed Europe PMC Scholia
  30. Hemoglobin variants and determination of glycated hemoglobin (HbA1c). Schnedl WJ, Liebminger A, Roller RE, Lipp RW, Krejs GJ. Diabetes Metab Res Rev. 2001;17(2):94–8. PubMed Europe PMC Scholia
  31. Homocysteine induces programmed cell death in human vascular endothelial cells through activation of the unfolded protein response. Zhang C, Cai Y, Adachi MT, Oshiro S, Aso T, Kaufman RJ, et al. J Biol Chem. 2001 Sep 21;276(38):35867–74. PubMed Europe PMC Scholia
  32. Reactive oxygen species-induced phosphorylation of p53 on serine 20 is mediated in part by polo-like kinase-3. Xie S, Wang Q, Wu H, Cogswell J, Lu L, Jhanwar-Uniyal M, et al. J Biol Chem. 2001 Sep 28;276(39):36194–9. PubMed Europe PMC Scholia
  33. Elements of the fibrinolytic system. Lijnen HR. Ann N Y Acad Sci. 2001;936:226–36. PubMed Europe PMC Scholia
  34. Determinants of cobalamin status in newborns. Bjørke Monsen AL, Ueland PM, Vollset SE, Guttormsen AB, Markestad T, Solheim E, et al. Pediatrics. 2001 Sep;108(3):624–30. PubMed Europe PMC Scholia
  35. The covalent FAD of monoamine oxidase: structural and functional role and mechanism of the flavinylation reaction. Edmondson DE, Newton-Vinson P. Antioxid Redox Signal. 2001 Oct;3(5):789–806. PubMed Europe PMC Scholia
  36. The effects of folate supplementation on some coagulation parameters and oxidative status surrogates. Mayer O Jr, Simon J, Rosolová H, Hromádka M, Subrt I, Vobrubová I. Eur J Clin Pharmacol. 2002 Apr;58(1):1–5. PubMed Europe PMC Scholia
  37. Effect of riboflavin supplementation on plasma homocysteine in elderly people with low riboflavin status. McKinley MC, McNulty H, McPartlin J, Strain JJ, Scott JM. Eur J Clin Nutr. 2002 Sep;56(9):850–6. PubMed Europe PMC Scholia
  38. Prostaglandin E synthase. Murakami M, Nakatani Y, Tanioka T, Kudo I. Prostaglandins Other Lipid Mediat. 2002 Aug;68–69:383–99. PubMed Europe PMC Scholia
  39. Prostaglandin F synthase. Watanabe K. Prostaglandins Other Lipid Mediat. 2002 Aug;68–69:401–7. PubMed Europe PMC Scholia
  40. Thromboxane synthase: structure and function of protein and gene. Wang LH, Kulmacz RJ. Prostaglandins Other Lipid Mediat. 2002 Aug;68–69:409–22. PubMed Europe PMC Scholia
  41. Folate: a key to optimizing health and reducing disease risk in the elderly. Rampersaud GC, Kauwell GPA, Bailey LB. J Am Coll Nutr. 2003 Feb;22(1):1–8. PubMed Europe PMC Scholia
  42. Folic acid says NO to vascular diseases. Das UN. Nutrition. 2003;19(7–8):686–92. PubMed Europe PMC Scholia
  43. 5-lipoxygenase and FLAP. Peters-Golden M, Brock TG. Prostaglandins Leukot Essent Fatty Acids. 2003;69(2–3):99–109. PubMed Europe PMC Scholia
  44. Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism. Karthikeyan S, Zhou Q, Osterman AL, Zhang H. Biochemistry. 2003 Nov 4;42(43):12532–8. PubMed Europe PMC Scholia
  45. A study on soluble intercellular adhesion molecule-1 and selenium in patients with rheumatoid arthritis complicated by vasculitis. Witkowska AM, Kuryliszyn-Moskal A, Borawska MH, Hukałowicz K, Markiewicz R. Clin Rheumatol. 2003 Dec;22(6):414–9. PubMed Europe PMC Scholia
  46. Molecular basis of homocysteine toxicity in humans. Jakubowski H. Cell Mol Life Sci. 2004 Feb;61(4):470–87. PubMed Europe PMC Scholia
  47. Endothelial function in post-menopausal women: effect of folic acid supplementation. Paradisi G, Cucinelli F, Mele MC, Barini A, Lanzone A, Caruso A. Hum Reprod. 2004 Apr;19(4):1031–5. PubMed Europe PMC Scholia
  48. Apolipoprotein A-I is a selective target for myeloperoxidase-catalyzed oxidation and functional impairment in subjects with cardiovascular disease. Zheng L, Nukuna B, Brennan ML, Sun M, Goormastic M, Settle M, et al. J Clin Invest. 2004 Aug;114(4):529–41. PubMed Europe PMC Scholia
  49. Diet and lifestyle are associated with serum C-reactive protein concentrations in a population-based study. Bertran N, Camps J, Fernandez-Ballart J, Arija V, Ferre N, Tous M, et al. J Lab Clin Med. 2005 Jan;145(1):41–6. PubMed Europe PMC Scholia
  50. Methionine oxidation by reactive oxygen species: reaction mechanisms and relevance to Alzheimer’s disease. Schöneich C. Biochim Biophys Acta. 2005 Jan 17;1703(2):111–9. PubMed Europe PMC Scholia
  51. Myeloperoxidase: friend and foe. Klebanoff SJ. J Leukoc Biol. 2005 May;77(5):598–625. PubMed Europe PMC Scholia
  52. Identification of amino acids required for the functional up-regulation of human dihydrofolate reductase protein in response to antifolate Treatment. Skacel N, Menon LG, Mishra PJ, Peters R, Banerjee D, Bertino JR, et al. J Biol Chem. 2005 Jun 17;280(24):22721–31. PubMed Europe PMC Scholia
  53. Fibrinogen and fibrin. Weisel JW. Adv Protein Chem. 2005;70:247–99. PubMed Europe PMC Scholia
  54. New insights into the regulation of HDL metabolism and reverse cholesterol transport. Lewis GF, Rader DJ. Circ Res. 2005 Jun 24;96(12):1221–32. PubMed Europe PMC Scholia
  55. Serum amyloid A promotes cholesterol efflux mediated by scavenger receptor B-I. van der Westhuyzen DR, Cai L, de Beer MC, de Beer FC. J Biol Chem. 2005 Oct 28;280(43):35890–5. PubMed Europe PMC Scholia
  56. The serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble gp130 (sgp130) in different tumour stages. Correlation between the two parameters in progression of malignancy. Kovacs E. Biomed Pharmacother. 2005 Oct;59(9):498–500. PubMed Europe PMC Scholia
  57. Myeloperoxidase metabolizes thiocyanate in a reaction driven by nitric oxide. Galijasevic S, Saed GM, Hazen SL, Abu-Soud HM. Biochemistry. 2006 Jan 31;45(4):1255–62. PubMed Europe PMC Scholia
  58. Modification of low-density lipoprotein by myeloperoxidase-derived oxidants and reagent hypochlorous acid. Malle E, Marsche G, Arnhold J, Davies MJ. Biochim Biophys Acta. 2006 Apr;1761(4):392–415. PubMed Europe PMC Scholia
  59. NF-kappaB1 (p50) homodimers differentially regulate pro- and anti-inflammatory cytokines in macrophages. Cao S, Zhang X, Edwards JP, Mosser DM. J Biol Chem. 2006 Sep 8;281(36):26041–50. PubMed Europe PMC Scholia
  60. Regulation of p53 tumour suppressor target gene expression by the p52 NF-kappaB subunit. Schumm K, Rocha S, Caamano J, Perkins ND. EMBO J. 2006 Oct 18;25(20):4820–32. PubMed Europe PMC Scholia
  61. Insulin resistance and oxidative stress interdependency in non-alcoholic fatty liver disease. Videla LA, Rodrigo R, Araya J, Poniachik J. Trends Mol Med. 2006 Dec;12(12):555–8. PubMed Europe PMC Scholia
  62. Glutathione peroxidases and redox-regulated transcription factors. Brigelius-Flohé R. Biol Chem. 2006;387(10–11):1329–35. PubMed Europe PMC Scholia
  63. Human glycinamide ribonucleotide transformylase: active site mutants as mechanistic probes. Manieri W, Moore ME, Soellner MB, Tsang P, Caperelli CA. Biochemistry. 2007 Jan 9;46(1):156–63. PubMed Europe PMC Scholia
  64. Association between the intake of vitamins and trace elements from supplements and C-reactive protein: results of the MONICA/KORA Augsburg study. Scheurig AC, Thorand B, Fischer B, Heier M, Koenig W. Eur J Clin Nutr. 2008 Jan;62(1):127–37. PubMed Europe PMC Scholia
  65. Removal of triacylglycerols from chylomicrons and VLDL by capillary beds: the basis of lipoprotein remnant formation. Karpe F, Bickerton AS, Hodson L, Fielding BA, Tan GD, Frayn KN. Biochem Soc Trans. 2007 Jun;35(Pt 3):472–6. PubMed Europe PMC Scholia
  66. Properties of an unusual heme cofactor in PLP-dependent cystathionine beta-synthase. Singh S, Madzelan P, Banerjee R. Nat Prod Rep. 2007 Jun;24(3):631–9. PubMed Europe PMC Scholia
  67. Rosiglitazone attenuates NF-kappaB-dependent ICAM-1 and TNF-alpha production caused by homocysteine via inhibiting ERK1/2/p38MAPK activation. Bai YP, Liu YH, Chen J, Song T, You Y, Tang ZY, et al. Biochem Biophys Res Commun. 2007 Aug 17;360(1):20–6. PubMed Europe PMC Scholia
  68. Glucose metabolism and catecholamines. Barth E, Albuszies G, Baumgart K, Matejovic M, Wachter U, Vogt J, et al. Crit Care Med. 2007 Sep;35(9 Suppl):S508-18. PubMed Europe PMC Scholia
  69. Serum selenium concentrations correlate significantly with inflammatory biomarker high-sensitive CRP levels in Hungarian gestational diabetic and healthy pregnant women at mid-pregnancy. Molnar J, Garamvolgyi Z, Herold M, Adanyi N, Somogyi A, Rigo J Jr. Biol Trace Elem Res. 2008 Jan;121(1):16–22. PubMed Europe PMC Scholia
  70. Structures of prostacyclin synthase and its complexes with substrate analog and inhibitor reveal a ligand-specific heme conformation change. Li YC, Chiang CW, Yeh HC, Hsu PY, Whitby FG, Wang LH, et al. J Biol Chem. 2008 Feb 1;283(5):2917–26. PubMed Europe PMC Scholia
  71. Plasma S-adenosylhomocysteine is a better biomarker of atherosclerosis than homocysteine in apolipoprotein E-deficient mice fed high dietary methionine. Liu C, Wang Q, Guo H, Xia M, Yuan Q, Hu Y, et al. J Nutr. 2008 Feb;138(2):311–5. PubMed Europe PMC Scholia
  72. Roles of MAPK and NF-kappaB in interleukin-6 induction by lipopolysaccharide in vascular smooth muscle cells. Son YH, Jeong YT, Lee KA, Choi KH, Kim SM, Rhim BY, et al. J Cardiovasc Pharmacol. 2008 Jan;51(1):71–7. PubMed Europe PMC Scholia
  73. Cyclooxygenase and prostaglandin synthases in atherosclerosis: recent insights and future perspectives. Cipollone F, Cicolini G, Bucci M. Pharmacol Ther. 2008 May;118(2):161–80. PubMed Europe PMC Scholia
  74. Evolution of catalases from bacteria to humans. Zamocky M, Furtmüller PG, Obinger C. Antioxid Redox Signal. 2008 Sep;10(9):1527–48. PubMed Europe PMC Scholia
  75. F2-isoprostanes in human health and diseases: from molecular mechanisms to clinical implications. Basu S. Antioxid Redox Signal. 2008 Aug;10(8):1405–34. PubMed Europe PMC Scholia
  76. The proton-coupled folate transporter: impact on pemetrexed transport and on antifolates activities compared with the reduced folate carrier. Zhao R, Qiu A, Tsai E, Jansen M, Akabas MH, Goldman ID. Mol Pharmacol. 2008 Sep;74(3):854–62. PubMed Europe PMC Scholia
  77. Association between dietary fiber and markers of systemic inflammation in the Women’s Health Initiative Observational Study. Ma Y, Hébert JR, Li W, Bertone-Johnson ER, Olendzki B, Pagoto SL, et al. Nutrition. 2008 Oct;24(10):941–9. PubMed Europe PMC Scholia
  78. Oxidative stress in normal and impaired wound repair. Schäfer M, Werner S. Pharmacol Res. 2008 Aug;58(2):165–71. PubMed Europe PMC Scholia
  79. FoxO1 integrates insulin signaling to VLDL production. Kamagate A, Dong HH. Cell Cycle. 2008 Oct;7(20):3162–70. PubMed Europe PMC Scholia
  80. Oxidative modification of LDL: its pathological role in atherosclerosis. Itabe H. Clin Rev Allergy Immunol. 2009 Aug;37(1):4–11. PubMed Europe PMC Scholia
  81. Fructosamine--an underutilized tool in diabetes management: case report and literature review. Youssef D, El Abbassi A, Jordan RM, Peiris AN. Tenn Med. 2008 Nov;101(11):31–3. PubMed Europe PMC Scholia
  82. Genetic variants in phosphatidylethanolamine N-methyltransferase and methylenetetrahydrofolate dehydrogenase influence biomarkers of choline metabolism when folate intake is restricted. Ivanov A, Nash-Barboza S, Hinkis S, Caudill MA. J Am Diet Assoc. 2009 Feb;109(2):313–8. PubMed Europe PMC Scholia
  83. Structure and mechanism of a eukaryotic FMN adenylyltransferase. Huerta C, Borek D, Machius M, Grishin NV, Zhang H. J Mol Biol. 2009 Jun 5;389(2):388–400. PubMed Europe PMC Scholia
  84. Studies of biomarker responses to intervention with riboflavin: a systematic review. Hoey L, McNulty H, Strain JJ. Am J Clin Nutr. 2009 Jun;89(6):1960S-1980S. PubMed Europe PMC Scholia
  85. Should D-dimer testing be used to predict the risk of recurrence after discontinuation of anticoagulant therapy for a first unprovoked episode of venous thromboembolism? Wu C, Bates SM. Pol Arch Med Wewn. 2009 Apr;119(4):225–30. PubMed Europe PMC Scholia
  86. Protein tyrosine nitration: selectivity, physicochemical and biological consequences, denitration, and proteomics methods for the identification of tyrosine-nitrated proteins. Abello N, Kerstjens HAM, Postma DS, Bischoff R. J Proteome Res. 2009 Jul;8(7):3222–38. PubMed Europe PMC Scholia
  87. Role of the MTHFR polymorphisms in cancer risk modification and treatment. Kim YI. Future Oncol. 2009 May;5(4):523–42. PubMed Europe PMC Scholia
  88. Human S-adenosylhomocysteine hydrolase: common gene sequence variation and functional genomic characterization. Feng Q, Keshtgarpour M, Pelleymounter LL, Moon I, Kalari KR, Eckloff BW, et al. J Neurochem. 2009 Sep;110(6):1806–17. PubMed Europe PMC Scholia
  89. Folate/homocysteine phenotypes and MTHFR 677C>T genotypes are associated with serum levels of monocyte chemoattractant protein-1. Hammons AL, Summers CM, Woodside JV, McNulty H, Strain JJ, Young IS, et al. Clin Immunol. 2009 Oct;133(1):132–7. PubMed Europe PMC Scholia
  90. Tetrahydrobiopterin, superoxide, and vascular dysfunction. Vásquez-Vivar J. Free Radic Biol Med. 2009 Oct 15;47(8):1108–19. PubMed Europe PMC Scholia
  91. Review article: Coagulation cascade and therapeutics update: relevance to nephrology. Part 1: Overview of coagulation, thrombophilias and history of anticoagulants. Adams RLC, Bird RJ. Nephrology (Carlton). 2009 Aug;14(5):462–70. PubMed Europe PMC Scholia
  92. The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake. Bailey SW, Ayling JE. Proc Natl Acad Sci U S A. 2009 Sep 8;106(36):15424–9. PubMed Europe PMC Scholia
  93. Reversible severe combined immunodeficiency phenotype secondary to a mutation of the proton-coupled folate transporter. Borzutzky A, Crompton B, Bergmann AK, Giliani S, Baxi S, Martin M, et al. Clin Immunol. 2009 Dec;133(3):287–94. PubMed Europe PMC Scholia
  94. Proinflammatory cytokines in CRP baseline regulation. Eklund CM. Adv Clin Chem. 2009;48:111–36. PubMed Europe PMC Scholia
  95. p53 and the regulation of hepatocyte apoptosis: implications for disease pathogenesis. Amaral JD, Castro RE, Steer CJ, Rodrigues CMP. Trends Mol Med. 2009 Nov;15(11):531–41. PubMed Europe PMC Scholia
  96. Associations of plasma homocysteine level with brachial-ankle pulse wave velocity, LDL atherogenicity, and inflammation profile in healthy men. Yun J, Kim JY, Kim OY, Jang Y, Chae JS, Kwak JH, et al. Nutr Metab Cardiovasc Dis. 2011 Feb;21(2):136–43. PubMed Europe PMC Scholia
  97. Folate receptor beta is expressed by tumor-associated macrophages and constitutes a marker for M2 anti-inflammatory/regulatory macrophages. Puig-Kröger A, Sierra-Filardi E, Domínguez-Soto A, Samaniego R, Corcuera MT, Gómez-Aguado F, et al. Cancer Res. 2009 Dec 15;69(24):9395–403. PubMed Europe PMC Scholia