FOLATE CYCLE METABOLIC PATHWAY (PW:0001207)

View Ontology Report

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. 5-methyl-THF Cbl Mtr polyGluTHF ---> monoGluTHF Folh1 uptaken folate ---> Slc25a32 diet/supplement THF 5,10-methylene-THF folate mediated one-carbon metabolic pathway methionine cycle/metabolic pathway homocysteine metabolic pathway mTHF sarcosine ---> 5,10-methylene-THF dimethylglycine ---> 5,10-methylene-THF mSer ---> 5,10-methylene-THF mGly ---> 5,10-methylene-THF mGly GCS CO2 sarcosine mSer dimethylglycine 5,10-methenyl-THF 10-formyl-THF formate PLP/B6 serine serine ---> 5,10-methylene-THF 5,10-methylene-THF <--> THF FAD Mtrr glutamate(s) DHF uptaken folate folate monoGluTHF polyGluTHF Shmt1 DHF ---> THF 10-formyl-THF ---- CO2 monoGluTHF ---> folate 5,10-methenyl-THF ---> 10-formyl-THF Mthfd2l uptaken folate ---> DHF 10-formyl-THF ---> formate 5,10-methylene-THF ---> 5,10-methenyl-THF 5,10-methenyl-THF ---> 5,10-methylene-THF 10-formyl-THF ---> 5,10-methenyl-THF formate ---> 10-formyl-THF 5-methyl-THF ---> THF THF ---> glutamate(s) Ggh glutamate(s) ---> THF Fpgs Slc25a32 Shmt2 diet/supplement ---> polyGluTHF Slc46a1 Sardh 10-formyl-THF ---> THF Mthfd1 Dhfr 5,10-methylene-THF ---> 5-methyl-THF Mthfr folate ---> uptaken folate Slc19a1 Folr2 Folr1 Mthfd1l Aldh1l1 Dmgdh THF ---> 10-formyl-THF Mthfd2 Mtrr ---> Mtr
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Genes in Pathway:

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folate cycle metabolic pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Aldh1l1 aldehyde dehydrogenase 1 family, member L1 JBrowse link 4 123,516,553 123,564,067 RGD:7242562
G Amt aminomethyltransferase JBrowse link 8 117,068,388 117,078,633 RGD:7242560
G Dhfr dihydrofolate reductase JBrowse link 2 21,931,887 21,958,927 RGD:7242557
G Dld dihydrolipoamide dehydrogenase JBrowse link 6 50,597,677 50,618,694 RGD:7242560
G Dmgdh dimethylglycine dehydrogenase JBrowse link 2 23,289,376 23,370,360 RGD:7242560
G Folh1 folate hydrolase 1 JBrowse link 1 150,323,768 150,395,415 RGD:7242426
RGD:7242559
G Folr1 folate receptor 1 JBrowse link 1 166,934,457 166,945,864 RGD:7242557
G Folr2 folate receptor beta JBrowse link 1 166,915,045 166,933,377 RGD:7242557
G Fpgs folylpolyglutamate synthase JBrowse link 3 11,717,667 11,729,694 RGD:7242559
G Gcsh glycine cleavage system protein H JBrowse link 19 49,522,054 49,532,811 RGD:7242560
G Ggh gamma-glutamyl hydrolase JBrowse link 5 34,040,258 34,063,369 RGD:7242559
G Gldc glycine decarboxylase JBrowse link 1 248,295,140 248,377,122 RGD:7242560
G Mthfd1 methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1 JBrowse link 6 99,282,850 99,350,367 RGD:7242557
G Mthfd1l methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like JBrowse link 1 40,529,092 40,719,232 RGD:7242557
G Mthfd2 methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase JBrowse link 4 115,004,433 115,015,965 RGD:7242557
RGD:7242560
G Mthfd2l methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2-like JBrowse link 14 18,640,274 18,721,298 RGD:7242557
G Mthfr methylenetetrahydrofolate reductase JBrowse link 5 164,844,642 164,864,360 RGD:7242557
G Mtr 5-methyltetrahydrofolate-homocysteine methyltransferase JBrowse link 17 66,210,444 66,295,014 RGD:7242557
G Mtrr 5-methyltetrahydrofolate-homocysteine methyltransferase reductase JBrowse link 1 37,743,089 37,774,485 RGD:7242557
G Sardh sarcosine dehydrogenase JBrowse link 3 5,737,203 5,802,153 RGD:7242560
G Shmt1 serine hydroxymethyltransferase 1 JBrowse link 10 47,030,813 47,059,216 RGD:7242557
G Shmt2 serine hydroxymethyltransferase 2 JBrowse link 7 70,824,718 70,829,822 RGD:7242557
RGD:7242560
G Slc19a1 solute carrier family 19 member 1 JBrowse link 20 12,334,675 12,354,517 RGD:7242426
RGD:7242557
G Slc25a32 solute carrier family 25 member 32 JBrowse link 7 77,983,885 78,005,058 RGD:7242561
G Slc46a1 solute carrier family 46 member 1 JBrowse link 10 65,728,508 65,741,708 RGD:7242426
RGD:7242557
altered folate cycle metabolic pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Aldh1l1 aldehyde dehydrogenase 1 family, member L1 JBrowse link 4 123,516,553 123,564,067 RGD:7242562
G Dhfr dihydrofolate reductase JBrowse link 2 21,931,887 21,958,927 RGD:7242557
G Folr1 folate receptor 1 JBrowse link 1 166,934,457 166,945,864 RGD:7242557
G Mthfd1 methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1 JBrowse link 6 99,282,850 99,350,367 RGD:7242557
G Mthfr methylenetetrahydrofolate reductase JBrowse link 5 164,844,642 164,864,360 RGD:7242557
G Mtr 5-methyltetrahydrofolate-homocysteine methyltransferase JBrowse link 17 66,210,444 66,295,014 RGD:7242557
G Mtrr 5-methyltetrahydrofolate-homocysteine methyltransferase reductase JBrowse link 1 37,743,089 37,774,485 RGD:7242557
G Slc46a1 solute carrier family 46 member 1 JBrowse link 10 65,728,508 65,741,708 RGD:7242557

Altered Pathway:

Additional Elements in Pathway:

(includes Gene Groups, Small Molecules, Other Pathways..etc.)
Object TypePathway ObjectPathway Object Description
ComplexGCS complexThe mitochondrial multi-subunit glycine cleavage system

Pathway Gene Annotations

Disease Annotations Associated with Genes in the folate cycle metabolic pathway
Disease TermsGene Symbols
Abortion, HabitualMthfr
Abortion, SpontaneousDhfr
Abruptio PlacentaeMthfd1
AcidosisAmt
Acute Kidney InjuryMthfr
AdenomaMtrr , Slc19a1
AlbuminuriaMthfr
AlopeciaMthfr
Alzheimer DiseaseMthfr
Amino Acid Metabolism, Inborn ErrorsGcsh
Amyotrophic Lateral SclerosisMthfr
Amyotrophic Lateral Sclerosis 1Folh1
AnemiaMthfr , Slc46a1
Anemia, MegaloblasticDhfr
Anemia, Sickle CellMthfr
AnencephalyMtrr
AnoxiaAldh1l1 , Sardh
Aortic Aneurysm, AbdominalMthfr
Aortic CoarctationMthfr
Arakawa Syndrome 2Mtr
Arsenic PoisoningMthfr
Arterial Occlusive DiseasesMthfr
Arthritis, RheumatoidDhfr , Fpgs , Ggh , Mthfr
AsthmaMthfr
AtherosclerosisMthfr
Attention Deficit Disorder with HyperactivityMthfr
Autistic DisorderDhfr , Mthfr , Mtr , Slc19a1
Bipolar DisorderMthfr
Blood Coagulation Disorders, InheritedMthfr
Brain Diseases, Metabolic, InbornFolr1
Brain IschemiaMthfr
Breast NeoplasmsDhfr , Mthfr , Mtr , Shmt1
Budd-Chiari SyndromeMthfr
Carcinoma, HepatocellularMthfd2
Carcinoma, Non-Small-Cell LungShmt2
Carcinoma, Renal CellMthfr
Carcinoma, Squamous CellMthfr
Carcinoma, Transitional CellGgh , Mthfr
Cardiac Valvular Defect, DevelopmentalMthfd1
Cardiovascular DiseasesMthfr
Carotid StenosisMthfr
CataractMthfr , Slc19a1
Cerebral InfarctionMthfr
Cervical Intraepithelial NeoplasiaMthfr
CholangiocarcinomaMthfr
Clear-Cell Metastatic Renal Cell CarcinomaMthfr
Cleft LipMthfd1 , Mthfr , Mtr , Slc19a1
Cleft PalateMthfd1 , Mtr , Slc19a1
ClubfootMthfr
Colonic NeoplasmsFolr1 , Mthfr , Slc19a1
Colorectal NeoplasmsDhfr , Fpgs , Ggh , Mthfr , Mtrr , Slc19a1
Congenital AbnormalitiesFolr1
Conotruncal Cardiac DefectsMthfr
Coronary Artery DiseaseMthfr
Coronary DiseaseMthfr
Coronary RestenosisMthfr
Craniofacial AbnormalitiesFolr1 , Mthfd1l
Depressive DisorderMthfr
Diabetes Mellitus, ExperimentalMthfr , Mtr
Diabetes Mellitus, Type 1Mthfr
Diabetes Mellitus, Type 2Mthfr , Mtr
Diabetic AngiopathiesMthfr
Diabetic NephropathiesMthfr , Mtrr
Diabetic RetinopathyMthfr
Dimethylglycine Dehydrogenase DeficiencyDmgdh
Down SyndromeMthfd1 , Mthfr , Mtrr , Slc19a1
Drug EruptionsMthfr
Drug-Induced Liver InjuryDhfr , Ggh , Mthfr
Drug-Related Side Effects and Adverse ReactionsDhfr , Mthfr , Mtr , Mtrr , Shmt1 , Slc19a1
Endometrial NeoplasmsMthfr
EpilepsyFolr1 , Mtr
Epilepsy, GeneralizedFolr1
Exercise IntoleranceSlc25a32
Eye DiseasesMthfr
Fatty LiverMthfr
Fetal Growth RetardationMthfd1
Folate Malabsorption, HereditarySlc46a1
Folic Acid DeficiencyDhfr
Gastrointestinal DiseasesMthfr , Mtr
Gastrointestinal Stromal TumorsDhfr , Folr1 , Mthfr , Mtr , Mtrr , Shmt1 , Slc19a1
Genetic Diseases, InbornMtr , Mtrr
Glaucoma, Angle-ClosureMthfr
Glaucoma, Open-AngleMthfr
GlomerulonephritisMthfr
Glomerulonephritis, IGAMtr
Graft vs Host DiseaseMthfr
Graves DiseaseMthfr
Hearing LossMthfr , Mtr
Hearing Loss, SuddenMthfr , Mtr
Heart Defects, CongenitalFolr1 , Mthfr
Heart DiseasesMtr , Mtrr
Heart Septal DefectsMtrr
Hematologic DiseasesMthfr , Mtr
Hematologic NeoplasmsMthfr
Hemophilia AMthfr
High MyopiaSlc19a1
Hodgkin DiseaseMthfd2
HomocystinuriaMthfr , Mtrr
Homocystinuria-Megaloblastic Anemia due to Defect in Cobalamin Metabolism, CblE Complementation TypeMtrr
HydrocephalusGldc
Hyperglycinemia, NonketoticAmt , Gcsh , Gldc
HyperhomocysteinemiaMthfr , Mtr , Mtrr , Slc46a1
HypersensitivityMthfr
HypertensionMtr
HyperthyroidismMthfr
HypopituitarismMthfr
HypothyroidismMthfr
Infertility, FemaleDhfr , Mthfr
Infertility, MaleMthfr , Mtr , Mtrr
Inflammatory Bowel Disease 11Mtrr
Inflammatory Bowel DiseasesMthfr
Intellectual DisabilityFolr1
IschemiaMthfr
Kidney DiseasesMthfr
Kidney Failure, ChronicMthfr
Kidney Reperfusion InjuryDhfr
Knobloch SyndromeSlc19a1
Lactic Acidosis, Congenital Infantile, Due To LAD DeficiencyDld
Leigh DiseaseDld
Leukemia, Lymphocytic, Chronic, B-CellMthfr
Leukemia, Myelogenous, Chronic, BCR-ABL PositiveMthfr
Leukemia, MyeloidDhfr
Leukemia, Myeloid, AcuteMthfr , Mtrr
LeukoencephalopathiesMthfr , Mtr
LeukopeniaMthfr
Liver Cirrhosis, ExperimentalAldh1l1 , Folr2 , Ggh , Slc46a1
Liver DiseasesMthfr
Liver NeoplasmsMthfr
Lung NeoplasmsMthfr
LymphomaMthfr , Mtr
Lymphoma, FollicularMthfr , Mtr
Lymphoma, Large B-Cell, DiffuseMthfr
Lymphoma, Non-HodgkinFpgs , Mthfr , Mtrr , Shmt1
Malabsorption SyndromesSlc46a1
MalnutritionMthfr , Mtr
Maple Syrup Urine DiseaseDld
Maxillofacial AbnormalitiesMthfr
Megaloblastic Anemia due to Dihydrofolate Reductase DeficiencyDhfr
Meniere DiseaseMthfr
MeningiomaMtrr
MeningomyeloceleMthfr
Metabolism, Inborn ErrorsDhfr , Mtr , Mtrr
Methylcobalamin Deficiency, CblG TypeMtr
Methylenetetrahydrofolate Reductase DeficiencyMthfr
Microsatellite InstabilityMthfr
Microvascular AnginaMthfr
Migraine DisordersMthfr
Migraine with AuraMthfr
Movement DisordersFolr1
Mthfr Deficiency, Thermolabile TypeMthfr
MucositisMthfr
Multiple MyelomaMthfr , Mtr , Mtrr
Myelodysplastic SyndromesMtrr
Myeloproliferative DisordersMthfr
Myocardial InfarctionMthfr
NecrosisMthfr
Neoplasm MetastasisDhfr , Mthfr
NephrosclerosisMthfr
Nervous System DiseasesDhfr , Mthfr , Mtrr , Shmt1 , Slc19a1
Neural Tube Defect, Folate-SensitiveMthfd1 , Mthfr , Mtr , Mtrr
Neural Tube DefectsFolr1 , Folr2 , Gldc , Mthfd1 , Mthfd1l , Mthfr
Neurodegeneration due to Cerebral Folate Transport DeficiencyFolr1
Neurodegenerative DiseasesSlc19a1
NeutropeniaMthfr
Nonarteritic Anterior Ischemic Optic NeuropathyMthfr
ObesityAldh1l1 , Gldc
Oral Squamous Cell CarcinomaMthfr
OsteonecrosisMthfr
OsteosarcomaDhfr , Folr1 , Mthfr
Ovarian NeoplasmsFolr1 , Shmt1
Pancreatic NeoplasmsMthfr , Mtr , Mtrr
PancytopeniaDhfr , Slc46a1
Parkinson DiseaseMtrr
Peripheral Arterial DiseaseMthfr
Pleomorphic Xanthoastrocytoma Dld
Precursor Cell Lymphoblastic Leukemia-LymphomaDhfr , Fpgs , Mthfr , Mtr , Mtrr , Slc19a1
Prostatic NeoplasmsFolh1 , Mthfr , Slc25a32
Psychomotor DisordersFolr1
Pulmonary EmbolismMthfr
Pyruvate Dehydrogenase Complex Deficiency DiseaseDld
Rectal NeoplasmsMthfr
RecurrenceSlc19a1
Renal InsufficiencyMthfr
Renal Insufficiency, ChronicMthfr , Slc19a1 , Slc46a1
Renal Vascular DiseasesMthfr
Retinal DiseasesMthfr
Retinal DystrophiesSlc19a1
Retinal Vein OcclusionMthfr
RetinoblastomaMtr
SarcosinemiaSardh
SchizophreniaMthfr
Sinus Thrombosis, IntracranialMthfr
Skin DiseasesMthfr
Small Cell Lung CarcinomaMthfr
Smith-Magenis SyndromeGldc , Shmt1 , Slc46a1
Spinal Cord DiseasesMthfr
Spinal DysraphismMthfd1 , Mthfr , Mtr , Mtrr
Stomach NeoplasmsGldc , Mthfr
Stomatitis, AphthousMthfr
StrokeMthfr
Temporomandibular Joint DisordersMtrr
Tetralogy of FallotMthfd1 , Mthfr
ThrombocytopeniaMthfr
ThrombophiliaMthfr
ThrombosisMthfr
Thrombotic MicroangiopathiesMthfr
ThyrotoxicosisMthfr
Transposition of Great VesselsMthfr , Slc19a1
Urinary Bladder NeoplasmsGgh , Mthfr , Mtr , Slc19a1
Uterine Cervical NeoplasmsMthfr
Vascular CalcificationMthfr
Vascular DiseasesMthfr
Venous ThromboembolismMthfr
Venous ThrombosisMthfr
Vitamin B 12 DeficiencyMtr
Wet Macular DegenerationMthfr
Wilms TumorMthfr
Pathway Annotations Associated with Genes in the folate cycle metabolic pathway
Pathway TermsGene Symbols
2-aminoadipic 2-oxoadipic aciduria disease pathwayDld
3-hydroxy-3-methylglutaryl-CoA lyase deficiency pathwayDld
3-hydroxyisobutyric aciduria pathwayDld
3-methylcrotonyl CoA carboxylase 1 deficiency pathwayDld
altered folate cycle metabolic pathwayAldh1l1 , Dhfr , Folr1 , Mthfd1 , Mthfr , Mtr , Mtrr , Slc46a1
altered folate mediated one-carbon metabolic pathwayMthfd1 , Mthfr , Mtr
carnitine biosynthetic pathwayShmt1
choline metabolic pathwayMtr
citric acid cycle pathwayDld
cyanoamino acid metabolic pathwayShmt1 , Shmt2
cysteine and methionine metabolic pathwayMtr
dihydropyrimidine dehydrogenase deficiency pathwayAmt , Dld , Dmgdh , Gldc , Sardh , Shmt1 , Shmt2
dimethylglycine dehydrogenase deficiency pathwayAmt , Dld , Dmgdh , Gldc , Sardh , Shmt1 , Shmt2
dopa responsive dystonia disease pathwayDhfr
endocytosis pathwayFolr1 , Folr2
folate cycle metabolic pathwayAldh1l1 , Amt , Dhfr , Dld , Dmgdh , Folh1 , Folr1 , Folr2 , Fpgs , Gcsh , Ggh , Gldc , Mthfd1 , Mthfd1l , Mthfd2 , Mthfd2l , Mthfr , Mtr , Mtrr , Sardh , Shmt1 , Shmt2 , Slc19a1 , Slc25a32 , Slc46a1
folate mediated one-carbon metabolic pathwayAldh1l1 , Amt , Dhfr , Dmgdh , Folh1 , Ggh , Mthfd1 , Mthfd1l , Mthfd2 , Mthfd2l , Mthfr , Mtr , Mtrr , Sardh , Shmt1 , Shmt2
folate metabolic pathwayAldh1l1 , Dhfr , Dmgdh , Folh1 , Folr2 , Fpgs , Ggh , Mthfd1 , Mthfd1l , Mthfd2 , Mthfr , Mtr , Mtrr , Sardh , Shmt1 , Shmt2 , Slc19a1 , Slc46a1
fumaric aciduria disease pathwayDld
gluconeogenesis pathwayDld
glutaric aciduria type I disease pathwayDld
glycine metabolic pathwayShmt1 , Shmt2
glycine N-methyltransferase deficiency pathwayMthfr , Mtr , Shmt1
glycine, serine and threonine metabolic pathwayAmt , Dld , Dmgdh , Gldc , Sardh , Shmt1 , Shmt2
glycolysis pathwayDld
glycolysis/gluconeogenesis pathwayDld
hereditary folate malabsorption disease pathwayAldh1l1 , Dhfr , Fpgs , Ggh , Mthfd1 , Mthfd1l , Mthfd2 , Mthfr , Slc46a1
homocysteine metabolic pathwayMthfr
homocystinuria disease pathwayMthfr , Mtr , Shmt1
hyperlysinemias disease pathwayDld
hypermethioninemia disease pathwayMthfr , Mtr , Shmt1
isobutyryl-CoA dehydrogenase deficiency pathwayDld
isovaleric acidemia disease pathwayDld
Leigh syndrome pathwayDld
lysine degradation pathwayDld
maple syrup urine disease pathwayDld
methionine adenosyltransferase deficiency pathwayMthfr , Mtr , Shmt1
methionine cycle/metabolic pathwayMthfr , Mtr , Mtrr , Shmt1
methotrexate pharmacodynamics pathwayAldh1l1 , Dhfr , Fpgs , Ggh , Mthfd1 , Mthfd1l , Mthfd2 , Mthfr , Slc46a1
methylenetetrahydrofolate reductase deficiency pathwayMthfr , Mtr , Shmt1
methylmalonate semialdehyde dehydrogenase deficiency pathwayDld
methylmalonic acidemia disease pathwayDld
mitochondrial complex II deficiency pathwayDld
nonketotic hyperglycinemia disease pathwayAmt , Dld , Dmgdh , Gldc , Sardh , Shmt1 , Shmt2
Nonketotic hyperglycinemia disease pathwayAmt , Dld , Dmgdh , Gldc , Sardh , Shmt1 , Shmt2
primary hyperoxaluria type 2 disease pathwayDld
propionic acidemia disease pathwayDld
pyrimidine metabolic pathwayDhfr
pyruvate dehydrogenase complex deficiency pathwayDld
pyruvate dehydrogenase E1 deficiency pathwayDld
pyruvate dehydrogenase E2 deficiency pathwayDld
pyruvate dehydrogenase E3 deficiency pathwayDld
pyruvate kinase deficiency pathwayDld
pyruvate metabolic pathwayDld
remethylation pathway of homocysteine metabolism - cobalamin dependentMthfr , Mtr , Mtrr
remethylation pathway of homocysteine metabolism - cobalamin independent, betaine dependentMtr
saccharopinuria disease pathwayDld
sarcosinemia disease pathwayAmt , Dld , Dmgdh , Gldc , Sardh , Shmt1 , Shmt2
Segawa syndrome pathwayDhfr
selenoamino acid metabolic pathwayMtr
type I 3-Methylglutaconic aciduria disease pathwayDld
type III 3-Methylglutaconic aciduria disease pathwayDld
valine, leucine and isoleucine degradation pathwayDld

References Associated with the folate cycle metabolic pathway:

Ontology Path Diagram:

paths to the root

Import into Pathway Studio: