FOLATE MEDIATED ONE-CARBON METABOLIC PATHWAY (PW:0000189)

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Description

Tetrahydrofolates (THF) are soluble forms of vitamin B9 that play essential roles in a number of metabolic pathways by mediating the transfer of 1-carbon (1C) units for the de novo synthesis of purines and thymidylates and for the re-methylation of homocysteine (Hcy) to methionine (Met). Humans cannot synthesize folate and must derive it from diet or as a supplement in the form of folic acid (FA). The folate/FA consist of three moieties: a pterin (pteridine) ring, a para aminobenzoyl group (PABA

Pathway Diagram:

Ariadne Genomics Inc. homocysteine ---> methionine homocysteine 5-methyl-THF S-adenosylmethionine methionine Cbl 5-methyl-THF ---> THF 10-formyl-THF ---> de novo purine biosynthetic pathway ADP <--> ATP THF DHF <--> THF 5,10-methylene-THF <--> THF PLP/B6 DHF <--> 5,10-methylene-THF dTMP <--> dUMP 10-formyl-THF <--> THF NADP+ NADPH FAD dUMP dTMP DHF 5,10-methylene-THF ---> 5-methyl-THF formate Dhfr Shmt2 Shmt1 Tyms Atic Gart folate cycle metabolic pathway 5,10-methylene-THF <--> 10-formyl-THF methyl group transfer  to carbon, nitrogen, oxygen or sulfur atoms on proteins, nucleic acids, carbohydrates, lipids, small molecules methionine cycle/metabolic pathway 5,10-methylene-THF DNA synthesis, DNA repair dTMP ---> DNA synthesis, DNA repair Mthfr Mtr Mtrr Mtrr ---> Mtr 10-formyl-THF de novo purine biosynthetic pathway remethylation pathway of homocysteine metabolism - cobalamin dependent remethylation pathway of homocysteine metabolism - cobalamin dependent <--> methionine cycle/metabolic pathway ATP ADP NADPH ---> NADP+ Mthfd1 formate ---> 10-formyl-THF
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folate mediated one-carbon metabolic pathway term browser
Symbol Object Name GBrowse Chr Start Stop Reference
G Aldh1l1 aldehyde dehydrogenase 1 family, member L1 GBrowse link 4 186,990,816 187,030,955 RGD:1547843
RGD:6907045
G Aldh1l2 aldehyde dehydrogenase 1 family, member L2 GBrowse link 7 26,506,321 26,555,206 RGD:6907045
G Amt aminomethyltransferase GBrowse link 8 116,421,237 116,427,437 RGD:6907045
G Atic 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase GBrowse link 9 78,636,339 78,656,387 RGD:70804
RGD:6907045
RGD:7242561
G Dhfr dihydrofolate reductase GBrowse link 2
2
41,137,784
41,162,308
41,149,417
41,162,496
RGD:1298877
RGD:6907045
RGD:7242561
G Dmgdh dimethylglycine dehydrogenase GBrowse link 2 42,469,950 42,545,633 RGD:1547831
G Folh1 folate hydrolase 1 GBrowse link 1 156,631,301 156,702,948 RGD:728645
G Ftcd formimidoyltransferase cyclodeaminase GBrowse link 20 14,965,126 14,978,635 RGD:6907045
G Gart phosphoribosylglycinamide formyltransferase GBrowse link 11 35,389,216 35,414,461 RGD:1547842
RGD:6907045
RGD:7242561
G Ggh gamma-glutamyl hydrolase (conjugase, folylpolygammaglutamyl hydrolase) GBrowse link 5 38,693,591 38,716,702 RGD:69845
G Gnmt glycine N-methyltransferase GBrowse link 9 15,471,889 15,475,241 RGD:1545057
G Mtfmt mitochondrial methionyl-tRNA formyltransferase GBrowse link 8 70,644,131 70,674,636 RGD:6907045
G Mthfd1 methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1, methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase GBrowse link 6 108,694,405 108,761,922 RGD:1299513
RGD:6907045
RGD:7242561
G Mthfd1l methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like GBrowse link 1 41,876,363 42,065,394 RGD:6907045
G Mthfd2 methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase GBrowse link 4 179,592,799 179,604,331 RGD:1540378
RGD:6907045
G Mthfd2l methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2-like GBrowse link 14 18,548,222 18,629,209 RGD:6907045
G Mthfr methylenetetrahydrofolate reductase (NAD(P)H) GBrowse link 5 168,502,556 168,522,350 RGD:1535021
RGD:6907045
RGD:7242561
G Mthfs 5,10-methenyltetrahydrofolate synthetase (5-formyltetrahydrofolate cyclo-ligase) GBrowse link 8 96,071,796 96,121,086 RGD:6907045
G Mtr 5-methyltetrahydrofolate-homocysteine methyltransferase GBrowse link 17 67,954,893 68,041,488 RGD:1359026
RGD:6907045
RGD:7242426
G Mtrr 5-methyltetrahydrofolate-homocysteine methyltransferase reductase GBrowse link 1 39,124,730 39,156,109 RGD:7242426
G RGD1564040 similar to methylenetetrahydrofolate dehydrogenase (NAD) (EC 1.5.1.15)/methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9) precursor GBrowse link 5 124,738,251 124,739,298 RGD:6907045
G Sardh sarcosine dehydrogenase GBrowse link 3 11,100,670 11,164,367 RGD:634034
G Shmt1 serine hydroxymethyltransferase 1 (soluble) GBrowse link 10 46,802,986 46,831,051 RGD:1359815
RGD:2300383
RGD:6907045
RGD:7242561
G Shmt2 serine hydroxymethyltransferase 2 (mitochondrial) GBrowse link 7 70,998,103 71,003,197 RGD:1359815
RGD:2300383
RGD:6907045
RGD:7242561
G Tyms thymidylate synthetase GBrowse link 9 121,368,418 121,381,493 RGD:1545055
RGD:6907045
RGD:7242561
altered folate mediated one-carbon metabolic pathway term browser
Symbol Object Name GBrowse Chr Start Stop Reference
G Mthfd1 methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1, methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase GBrowse link 6 108,694,405 108,761,922 RGD:7242562
G Mthfr methylenetetrahydrofolate reductase (NAD(P)H) GBrowse link 5 168,502,556 168,522,350 RGD:7242562
G Mtr 5-methyltetrahydrofolate-homocysteine methyltransferase GBrowse link 17 67,954,893 68,041,488 RGD:7242562

Altered Pathway:

Pathway Gene Annotations

Disease Annotations Associated with Genes in the folate mediated one-carbon metabolic pathway
Disease TermsGene Symbols
Amyotrophic Lateral SclerosisFolh1
Aortic CoarctationMthfr
Pancreatic NeoplasmsMtr , Mtrr , Mthfr
CataractMthfr
OsteosarcomaMthfr
Retinal DiseasesMthfr
IschemiaMthfr
Hearing LossMtr , Mthfr
Carcinoma, Renal CellMthfr
Renal InsufficiencyMthfr
HyperhomocysteinemiaMtr , Mthfr
Diabetes Mellitus, Type 2Mtr , Mthfr
CholangiocarcinomaMthfr
Liver NeoplasmsMthfr
Neural Tube DefectsMthfd1 , Mthfr
SplenomegalyTyms
Eye DiseasesMthfr
HypothyroidismMthfr
Fatty LiverMthfr
Ovarian NeoplasmsShmt1
Breast NeoplasmsShmt1
MeningiomaMtrr
Colitis, UlcerativeMtrr
Spinal DysraphismMtr , Mthfd1 , Mtrr
Wilms TumorMthfr
Kidney Failure, ChronicMthfr
Neural tube defect, folate-sensitiveMtr , Mthfr , Mtrr
Urinary Bladder NeoplasmsTyms , Mtr , Mthfr
Carcinoma, Squamous CellMthfr
Arthritis, RheumatoidMthfr
Diabetes Mellitus, Type 1Mthfr
Hyperglycinemia, NonketoticAmt
Migraine DisordersMthfr
ThrombophiliaMthfr
Colorectal NeoplasmsTyms
Temporomandibular Joint DisordersMtrr
Rectal NeoplasmsMthfr
HypertensionMtr
Purine-Pyrimidine Metabolism, Inborn ErrorsAtic
Parkinson DiseaseMtrr
SarcosinemiaSardh
Migraine with AuraMthfr
Carcinoma, HepatocellularMthfd2
Methylenetetrahydrofolate reductase deficiencyMthfr
HomocystinuriaMthfr , Mtrr
Glutamate formiminotransferase deficiencyFtcd
Heart Septal DefectsMtrr
Gastrointestinal Stromal TumorsDhfr , Mtr , Mtrr , Mthfr , Shmt1
AcidosisAmt
Cerebral InfarctionMthfr
Glomerulonephritis, IGAMtr
Clear-cell metastatic renal cell carcinomaMthfr
GlomerulonephritisMthfr
Vitamin B 12 DeficiencyMtr
AlbuminuriaMthfr
Heart DiseasesMtr , Mtrr
Arthritis, ExperimentalAtic
AsthmaMthfr
Autistic DisorderMtr
Carcinoma, Transitional CellMthfr
Cardiovascular DiseasesMthfr
Coronary Artery DiseaseMthfr
Hearing Loss, SuddenMtr , Mthfr
Diabetes Mellitus, ExperimentalMtr , Mthfr
Diabetic NephropathiesMthfr , Mtrr
Diabetic RetinopathyMthfr
Down SyndromeGart
Glaucoma, Open-AngleMthfr
Graft vs Host DiseaseMthfr
Graves DiseaseMthfr
HyperthyroidismMthfr
Thrombotic MicroangiopathiesMthfr
Venous ThrombosisMthfr
Renal Insufficiency, ChronicMthfr
Mammary Neoplasms, ExperimentalTyms
Meniere DiseaseMthfr
Myocardial InfarctionMthfr
NephrosclerosisMthfr
Retinal Vein OcclusionMthfr
RetinoblastomaMtr
SchizophreniaMthfr
Glaucoma, Angle-ClosureMthfr
Lymphoma, Large B-Cell, DiffuseMthfr
Carotid StenosisMthfr
Aortic Aneurysm, AbdominalMthfr
Microvascular AnginaMthfr
StrokeMthfr
AtherosclerosisMthfr
Small Cell Lung CarcinomaMthfr
Wet Macular DegenerationMthfr
Peripheral Arterial DiseaseMthfr
AICAR TRANSFORMYLASE/IMP CYCLOHYDROLASE DEFICIENCYAtic
Vascular CalcificationMthfr
Leigh Syndrome Due To Mitochondrial Complex I DeficiencyMtfmt
Glycine N-Methyltransferase DeficiencyGnmt
Megaloblastic Anemia due to Dihydrofolate Reductase DeficiencyDhfr
Dimethylglycine Dehydrogenase DeficiencyDmgdh
Methylcobalamin Deficiency, CblG TypeMtr
Homocystinuria-Megaloblastic Anemia due to Defect in Cobalamin Metabolism, CblE Complementation TypeMtrr
Mthfr Deficiency, Thermolabile TypeMthfr
Nonarteritic Anterior Ischemic Optic NeuropathyMthfr
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 15Mtfmt
Pathway Annotations Associated with Genes in the folate mediated one-carbon metabolic pathway

References Associated with the folate mediated one-carbon metabolic pathway:

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