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 Evidence Chr Start Stop Reference Source
G Aldh1l1 aldehyde dehydrogenase 1 family, member L1 TAS RGD:1547843 RGD
G Aldh1l1 aldehyde dehydrogenase 1 family, member L1 IEA RGD:6907045 KEGG
G Aldh1l2 aldehyde dehydrogenase 1 family, member L2 GBrowse link IEA 7 22,398,067 22,450,381 RGD:6907045 KEGG
G Amt aminomethyltransferase IEA RGD:6907045 KEGG
G Atic 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase GBrowse link IEA 9 70,676,744 70,696,865 RGD:6907045 KEGG
G Atic 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase GBrowse link IDA 9 70,676,744 70,696,865 RGD:70804 RGD
G Atic 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase GBrowse link ISS 9 70,676,744 70,696,865 RGD:7242561 RGD
G Dhfr dihydrofolate reductase GBrowse link IDA 2 22,607,093 22,828,487 RGD:1298877 RGD
G Dhfr dihydrofolate reductase GBrowse link IEA 2 22,607,093 22,828,487 RGD:6907045 KEGG
G Dhfr dihydrofolate reductase GBrowse link ISS 2 22,607,093 22,828,487 RGD:7242561 RGD
G Dmgdh dimethylglycine dehydrogenase GBrowse link TAS 2 23,976,563 24,052,766 RGD:1547831 RGD
G Folh1 folate hydrolase 1 GBrowse link TAS 1 142,936,379 143,010,358 RGD:728645 RGD
G Ftcd formimidoyltransferase cyclodeaminase GBrowse link IEA 20 12,470,291 12,483,807 RGD:6907045 KEGG
G Gart phosphoribosylglycinamide formyltransferase GBrowse link ISS 11 31,594,859 31,620,110 RGD:1547842 RGD
G Gart phosphoribosylglycinamide formyltransferase GBrowse link IEA 11 31,594,859 31,620,110 RGD:6907045 KEGG
G Gart phosphoribosylglycinamide formyltransferase GBrowse link ISS 11 31,594,859 31,620,110 RGD:7242561 RGD
G Ggh gamma-glutamyl hydrolase (conjugase, folylpolygammaglutamyl hydrolase) GBrowse link TAS 5 34,670,883 34,693,791 RGD:69845 RGD
G Gnmt glycine N-methyltransferase GBrowse link TAS 9 10,127,092 10,130,444 RGD:1545057 RGD
G Mtfmt mitochondrial methionyl-tRNA formyltransferase GBrowse link IEA 8 69,683,737 69,701,721 RGD:6907045 KEGG
G Mthfd1 methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1, methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase GBrowse link IEA 6 98,849,446 98,916,936 RGD:6907045 KEGG
G Mthfd1 methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1, methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase GBrowse link TAS 6 98,849,446 98,916,936 RGD:1299513 RGD
G Mthfd1 methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1, methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase GBrowse link ISS 6 98,849,446 98,916,936 RGD:7242561 RGD
G Mthfd1l methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like GBrowse link IEA 1 34,759,445 34,800,865 RGD:6907045 KEGG
G Mthfd2 methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase GBrowse link ISS 4 117,517,611 117,529,128 RGD:1540378 RGD
G Mthfd2 methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase GBrowse link IEA 4 117,517,611 117,529,128 RGD:6907045 KEGG
G Mthfd2l methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2-like GBrowse link IEA 14 18,585,147 18,665,534 RGD:6907045 KEGG
G Mthfr methylenetetrahydrofolate reductase (NAD(P)H) GBrowse link ISS 5 165,112,850 165,126,885 RGD:7242561 RGD
G Mthfr methylenetetrahydrofolate reductase (NAD(P)H) GBrowse link ISS 5 165,112,850 165,126,885 RGD:1535021 RGD
G Mthfr methylenetetrahydrofolate reductase (NAD(P)H) GBrowse link IEA 5 165,112,850 165,126,885 RGD:6907045 KEGG
G Mthfs 5,10-methenyltetrahydrofolate synthetase (5-formyltetrahydrofolate cyclo-ligase) GBrowse link IEA 8 94,058,605 94,108,277 RGD:6907045 KEGG
G Mtr 5-methyltetrahydrofolate-homocysteine methyltransferase GBrowse link IEA 17 68,782,708 68,867,101 RGD:6907045 KEGG
G Mtr 5-methyltetrahydrofolate-homocysteine methyltransferase GBrowse link IDA 17 68,782,708 68,867,101 RGD:1359026 RGD
G Mtr 5-methyltetrahydrofolate-homocysteine methyltransferase GBrowse link ISS 17 68,782,708 68,867,101 RGD:7242426 RGD
G Mtrr 5-methyltetrahydrofolate-homocysteine methyltransferase reductase GBrowse link ISS 17 5,086,219 5,118,086 RGD:7242426 RGD
G RGD1564040 similar to methylenetetrahydrofolate dehydrogenase (NAD) (EC 1.5.1.15)/methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9) precursor GBrowse link IEA 5 122,694,391 122,695,440 RGD:6907045 KEGG
G Sardh sarcosine dehydrogenase GBrowse link TAS 3 6,076,166 6,142,565 RGD:634034 RGD
G Shmt1 serine hydroxymethyltransferase 1 (soluble) GBrowse link TAS 10 46,936,605 46,964,779 RGD:1359815 RGD
G Shmt1 serine hydroxymethyltransferase 1 (soluble) GBrowse link IEA 10 46,936,605 46,964,779 RGD:6907045 KEGG
G Shmt1 serine hydroxymethyltransferase 1 (soluble) GBrowse link IDA 10 46,936,605 46,964,779 RGD:2300383 RGD
G Shmt1 serine hydroxymethyltransferase 1 (soluble) GBrowse link ISS 10 46,936,605 46,964,779 RGD:7242561 RGD
G Shmt2 serine hydroxymethyltransferase 2 (mitochondrial) GBrowse link TAS 7 67,494,470 67,499,540 RGD:1359815 RGD
G Shmt2 serine hydroxymethyltransferase 2 (mitochondrial) GBrowse link ISS 7 67,494,470 67,499,540 RGD:7242561 RGD
G Shmt2 serine hydroxymethyltransferase 2 (mitochondrial) GBrowse link IEA 7 67,494,470 67,499,540 RGD:6907045 KEGG
G Shmt2 serine hydroxymethyltransferase 2 (mitochondrial) GBrowse link IDA 7 67,494,470 67,499,540 RGD:2300383 RGD
G Tyms thymidylate synthetase GBrowse link IDA 9 112,604,912 112,617,706 RGD:1545055 RGD
G Tyms thymidylate synthetase GBrowse link IEA 9 112,604,912 112,617,706 RGD:6907045 KEGG
G Tyms thymidylate synthetase GBrowse link ISS 9 112,604,912 112,617,706 RGD:7242561 RGD
altered folate mediated one-carbon metabolic pathway term browser
Symbol Object Name GBrowse Evidence Chr Start Stop Reference Source
G Mthfd1 methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1, methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase GBrowse link ISS 6 98,849,446 98,916,936 RGD:7242562 RGD
G Mthfr methylenetetrahydrofolate reductase (NAD(P)H) GBrowse link ISS 5 165,112,850 165,126,885 RGD:7242562 RGD
G Mtr 5-methyltetrahydrofolate-homocysteine methyltransferase GBrowse link ISS 17 68,782,708 68,867,101 RGD:7242562 RGD

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
Metabolism, Inborn ErrorsDhfr , Mthfd1
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
Anemia, MegaloblasticDhfr
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
AcidosisAmt
Cerebral InfarctionMthfr
Macular DegenerationMthfr
Glomerulonephritis, IGAMtr
Clear-cell metastatic renal cell carcinomaMthfr
GlomerulonephritisMthfr
Abruptio PlacentaeMthfd1
AlbuminuriaMthfr
Heart DiseasesMtr , Mtrr
Arthritis, ExperimentalAtic
AsthmaMthfr
Autistic DisorderMtr
Carcinoma, Transitional CellMthfr
Cardiovascular DiseasesMthfr
Coronary Artery DiseaseMthfr
Hearing Loss, SuddenMthfr
Diabetes Mellitus, ExperimentalMtr , Mthfr
Diabetic NephropathiesMthfr , Mtrr
Diabetic RetinopathyMthfr
Down SyndromeGart
Folic Acid DeficiencyDhfr
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
SchizophreniaMthfr
Glaucoma, Angle-ClosureMthfr
Lymphoma, Large B-Cell, DiffuseMthfr
Carotid StenosisMthfr
Aortic Aneurysm, AbdominalMthfr
Microvascular AnginaMthfr
StrokeMthfr
AtherosclerosisMthfr
Small Cell Lung CarcinomaMthfr
Peripheral Arterial DiseaseMthfr
AICAR TRANSFORMYLASE/IMP CYCLOHYDROLASE DEFICIENCYAtic
Vascular CalcificationMthfr
Glycine N-Methyltransferase DeficiencyGnmt
Dimethylglycine Dehydrogenase DeficiencyDmgdh
Methylcobalamin Deficiency, CblG TypeMtr
Homocystinuria-Megaloblastic Anemia due to Defect in Cobalamin Metabolism, CblE Complementation TypeMtrr
Pathway Annotations Associated with Genes in the folate mediated one-carbon metabolic pathway
Pathway TermsGene Symbols
purine metabolic pathwayAtic , Gart
pyrimidine metabolic pathwayDhfr , Tyms
glycine, serine and threonine metabolic pathwayGnmt , Dmgdh , Sardh , Shmt2 , Shmt1 , Amt
methionine cycle/metabolic pathwayGnmt , Mtr , Mtrr , Mthfr
histidine metabolic pathwayFtcd
cyanoamino acid metabolic pathwayShmt2 , Shmt1
selenoamino acid metabolic pathwayMtr
folate metabolic pathwayDhfr , Ggh , Gnmt , Tyms , Atic , Folh1 , Dmgdh , Sardh , Mtr , Aldh1l1 , Mthfd1 , Shmt2 , Mtrr , Gart , Mthfr , Mthfd2 , Shmt1
folate mediated one-carbon metabolic pathwayDhfr , Ggh , Gnmt , Tyms , Atic , Ftcd , Folh1 , Dmgdh , Sardh , Mtr , Aldh1l1 , Mthfd1 , Mthfs , Mthfd1l , Shmt2 , Mtrr , Gart , Aldh1l2 , Mtfmt , Mthfr , Mthfd2l , Mthfd2 , Shmt1 , Amt , RGD1564040
homocysteine metabolic pathwayGnmt , Mthfr
remethylation pathway of homocysteine metabolism - cobalamin dependentMtr , Mtrr , Mthfr
glycine metabolic pathwayShmt2 , Shmt1
de novo purine biosynthetic pathwayAtic , Gart
cysteine and methionine metabolic pathwayMtr
aminoacyl-tRNA biosynthetic pathwayMtfmt
folate cycle metabolic pathwayDhfr , Ggh , Folh1 , Dmgdh , Sardh , Mtr , Aldh1l1 , Mthfd1 , Mthfd1l , Shmt2 , Mtrr , Mthfr , Mthfd2l , Mthfd2 , Shmt1 , Amt
altered folate cycle metabolic pathwayDhfr , Mtr , Aldh1l1 , Mthfd1 , Mthfr , Mtrr
altered folate mediated one-carbon metabolic pathwayMtr , Mthfd1 , Mthfr

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

Ontology Path Diagram:

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