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(6R,S)-methenyltetrahydrofolate + H2O
?
-
-
-
-
?
10-formyltetrahydrofolate
5,10-methenyltetrahydrofolate + H2O
-
-
-
-
r
5,10-methenyltetrahydrofolate + H2O
10-formyltetrahydrofolate
5,10-methenyltetrahydrofolate + H2O
10-formyltetrahydrofolate + ?
cyclodehydrolase activity of MTHFD1
-
-
r
5,10-methylenetetrahydrofolate + NADP+
5,10-methenyltetrahydrofolate + NADPH + H+
additional information
?
-
5,10-methenyltetrahydrofolate + H2O
10-formyltetrahydrofolate
-
-
-
-
?
5,10-methenyltetrahydrofolate + H2O
10-formyltetrahydrofolate
-
-
-
-
r
5,10-methenyltetrahydrofolate + H2O
10-formyltetrahydrofolate
-
-
-
?
5,10-methenyltetrahydrofolate + H2O
10-formyltetrahydrofolate
-
5,10-methenyltetrahydrofolate 5-hydrolase (decyclizing), EC 3.5.4.9, activity of the enzyme
-
-
r
5,10-methenyltetrahydrofolate + H2O
10-formyltetrahydrofolate
5,10-methenyltetrahydrofolate 5-hydrolase (decyclizing), EC 3.5.4.9, activity of the enzyme
-
-
r
5,10-methenyltetrahydrofolate + H2O
10-formyltetrahydrofolate
-
bifunctional enzyme exhibits dihydrogenase and cyclohydrolase activities
-
-
r
5,10-methenyltetrahydrofolate + H2O
10-formyltetrahydrofolate
-
trifunctional enzyme exhibits synthetase, dehydrogenase and cyclohydrolase activities
-
-
r
5,10-methylenetetrahydrofolate + NADP+
5,10-methenyltetrahydrofolate + NADPH + H+
-
methylenetetrahydrofolate dehydrogenase (NADP+), EC 1.5.1.5, activity of the enzyme
-
-
r
5,10-methylenetetrahydrofolate + NADP+
5,10-methenyltetrahydrofolate + NADPH + H+
methylenetetrahydrofolate dehydrogenase (NADP+), EC 1.5.1.5, activity of the enzyme
-
-
r
additional information
?
-
bifunctional enzyme, channeling efficiency
-
-
?
additional information
?
-
-
bifunctional enzyme, channeling efficiency
-
-
?
additional information
?
-
-
the enzyme has a bifunctional DC domain that binds NADP+ and one folate molecule within a single catalytic cleft being part of a trifunctional enzyme, substrate channeling with high efficiency independent of NADP+ substrate binding efficiency
-
-
?
additional information
?
-
-
enzyme deficiency by G1958A polymorphism is involved in spontaneous cervical artery dissections
-
-
?
additional information
?
-
-
trifunctional folate enzyme
-
-
?
additional information
?
-
MTHFD1 is a trifunctional enzyme that interconverts tetrahydrofolate derivatives for nucleotide synthesis
-
-
?
additional information
?
-
-
the conversion of formyl- to methylenehydrofolate is rate-limited by the slow conversion by the cyclohydrolase of formyl- to methenyltetrahydrofolate
-
-
?
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Adenocarcinoma of Lung
MTHFD2 promotes tumorigenesis and metastasis in lung adenocarcinoma by regulating AKT/GSK-3?/?-catenin signalling.
Adenocarcinoma, Bronchiolo-Alveolar
mRNAs and miRNAs in whole blood associated with lung hyperplasia, fibrosis, and bronchiolo-alveolar adenoma and adenocarcinoma after multi-walled carbon nanotube inhalation exposure in mice.
Adenoma
mRNAs and miRNAs in whole blood associated with lung hyperplasia, fibrosis, and bronchiolo-alveolar adenoma and adenocarcinoma after multi-walled carbon nanotube inhalation exposure in mice.
Anemia, Megaloblastic
Update and new concepts in vitamin responsive disorders of folate transport and metabolism.
Atrial Fibrillation
GCH1 attenuates cardiac autonomic nervous remodeling in canines with atrial-tachypacing via tetrahydrobiopterin pathway regulated by microRNA-206.
Atypical Hemolytic Uremic Syndrome
Update and new concepts in vitamin responsive disorders of folate transport and metabolism.
Brain Neoplasms
Activity of 5-formyl tetrahydrofolate cyclodehydrase and 5,10-methenyl tetrahydrofolate cyclohydrolase in primary brain tumors in children.
Breast Neoplasms
A candidate CpG SNP approach identifies a breast cancer associated ESR1-SNP.
Breast Neoplasms
High-throughput RNAi screening for novel modulators of vimentin expression identifies MTHFD2 as a regulator of breast cancer cell migration and invasion.
Breast Neoplasms
Increased MTHFD2 expression is associated with poor prognosis in breast cancer.
Breast Neoplasms
Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer.
Breast Neoplasms
MicroRNA-9 Inhibition of Cell Proliferation and Identification of Novel miR-9 Targets by Transcriptome Profiling in Breast Cancer Cells.
Breast Neoplasms
MTHFD2 facilitates breast cancer cell proliferation via the AKT signaling pathway.
Breast Neoplasms
Quantitative proteomics study of breast cancer cell lines isolated from a single patient: discovery of TIMM17A as a marker for breast cancer.
Breast Neoplasms
Suppression of MTHFD2 in MCF-7 Breast Cancer Cells Increases Glycolysis, Dependency on Exogenous Glycine, and Sensitivity to Folate Depletion.
Carcinogenesis
Cancer stem-like properties and gefitinib resistance are dependent on purine synthetic metabolism mediated by the mitochondrial enzyme MTHFD2.
Carcinogenesis
Modulation of Redox Homeostasis by Inhibition of MTHFD2 in Colorectal Cancer: Mechanisms and Therapeutic Implications.
Carcinogenesis
MTHFD2 promotes tumorigenesis and metastasis in lung adenocarcinoma by regulating AKT/GSK-3?/?-catenin signalling.
Carcinogenesis
The folate cycle enzyme MTHFD2 induces cancer immune evasion through PD-L1 up-regulation.
Carcinoma
Identification of MTHFD2 as a novel prognosis biomarker in esophageal carcinoma patients based on transcriptomic data and methylation profiling.
Carcinoma
MTHFD2 links RNA methylation to metabolic reprogramming in renal cell carcinoma.
Carcinoma
MTHFD2 Overexpression Predicts Poor Prognosis in Renal Cell Carcinoma and is Associated with Cell Proliferation and Vimentin-Modulated Migration and Invasion.
Carcinoma
The Prognostic Significance of Immune-Related Metabolic Enzyme MTHFD2 in Head and Neck Squamous Cell Carcinoma.
Carcinoma, Ehrlich Tumor
NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase from ascites tumor cells. Purification and properties.
Carcinoma, Hepatocellular
Methylenetetrahydrofolate dehydrogenase 2 overexpression is associated with tumor aggressiveness and poor prognosis in hepatocellular carcinoma.
Carcinoma, Hepatocellular
[The preliminary study on the function of methylenetetrahydrofolate dehydrogenase 2 in hepatocellular carcinoma].
Carcinoma, Non-Small-Cell Lung
Down-regulation of MTHFD2 inhibits NSCLC progression by suppressing cycle-related genes.
Carcinoma, Renal Cell
MTHFD2 links RNA methylation to metabolic reprogramming in renal cell carcinoma.
Carcinoma, Renal Cell
MTHFD2 Overexpression Predicts Poor Prognosis in Renal Cell Carcinoma and is Associated with Cell Proliferation and Vimentin-Modulated Migration and Invasion.
Carcinoma, Squamous Cell
The Prognostic Significance of Immune-Related Metabolic Enzyme MTHFD2 in Head and Neck Squamous Cell Carcinoma.
Cleft Palate
Is MTHFD1 polymorphism rs 2236225 (c.1958G>A) associated with the susceptibility of NSCL/P? A systematic review and meta-analysis.
Colorectal Neoplasms
Cisplatin inhibits SIRT3-deacetylation MTHFD2 to disturb cellular redox balance in colorectal cancer cell.
Colorectal Neoplasms
MicroRNA-33a-5p suppresses colorectal cancer cell growth by inhibiting MTHFD2.
Colorectal Neoplasms
Modulation of Redox Homeostasis by Inhibition of MTHFD2 in Colorectal Cancer: Mechanisms and Therapeutic Implications.
Colorectal Neoplasms
The effect of MTHFD2 on the proliferation and migration of colorectal cancer cell lines.
Congenital Abnormalities
A polymorphism, R653Q, in the trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase is a maternal genetic risk factor for neural tube defects: report of the Birth Defects Research Group.
Diabetes Mellitus
Proteasome-dependent degradation of guanosine 5'-triphosphate cyclohydrolase I causes tetrahydrobiopterin deficiency in diabetes mellitus.
Dyskinesias
Dopamine gene therapy for Parkinson's disease in a nonhuman primate without associated dyskinesia.
Dystonia
Arg(184)His mutant GTP cyclohydrolase I, causing recessive hyperphenylalaninemia, is responsible for dopa-responsive dystonia with parkinsonism: a case report.
Dystonia
Common and rare GCH1 variants are associated with Parkinson's disease.
Dystonia
Levodopa-responsive dystonia. GTP cyclohydrolase I or parkin mutations?
Dystonia
Metabolism of tetrahydrobiopterin: its relevance in monoaminergic neurons and neurological disorders.
Dystonia
Missense mutants inactivate guanosine triphosphate cyclohydrolase I in hereditary progressive dystonia.
Dystonia
Molecular mechanisms of hereditary progressive dystonia with marked diurnal fluctuation, Segawa's disease.
Dystonia
Mutant GTP cyclohydrolase I in autosomal dominant dystonia and recessive hyperphenylalaninemia.
Dystonia
[GTP cyclohydrolase 1-deficient dopa-responsive hereditary dystonia.]
Fibromyalgia
Identification of candidate genes associated with fibromyalgia susceptibility in southern Spanish women: the al-Ándalus project.
Glaucoma
Reduced Oxidative Phosphorylation and Increased Glycolysis in Human Glaucoma Lamina Cribrosa Cells.
Glioma
Glioma cells require one-carbon metabolism to survive glutamine starvation.
Glioma
MicroRNA-940 inhibits glioma progression by blocking mitochondrial folate metabolism through targeting of MTHFD2.
Glioma
The Identification of Key Genes and Pathways in Glioma by Bioinformatics Analysis.
Graft vs Host Disease
Cyclosporine and methotrexate-related pharmacogenomic predictors of acute graft-versus-host disease.
gtp cyclohydrolase i deficiency
Characterization of mouse and human GTP cyclohydrolase I genes. Mutations in patients with GTP cyclohydrolase I deficiency.
Hypertension
Enhanced activation of NAD(P)H: quinone oxidoreductase 1 attenuates spontaneous hypertension by improvement of endothelial nitric oxide synthase coupling via tumor suppressor kinase liver kinase B1/adenosine 5'-monophosphate-activated protein kinase-mediated guanosine 5'-triphosphate cyclohydrolase 1 preservation.
Hypertension
Gene transfer of human guanosine 5'-triphosphate cyclohydrolase I restores vascular tetrahydrobiopterin level and endothelial function in low renin hypertension.
Infarction, Middle Cerebral Artery
Neuroprotective Effect of DAHP via Antiapoptosis in Cerebral Ischemia.
Infections
Cerebrospinal fluid and serum neopterin and biopterin in D-retrovirus-infected rhesus macaques (Macaca mulatta): relationship to clinical and viral status.
Infections
Role of potential COVID-19 immune system associated genes and the potential pathways linkage with type-2 diabetes.
Intellectual Disability
Mental retardation with hyperfolic-acidemia not associated with formiminoglutamic-acciduria: cyclohydrolase deficiency syndrome.
Intervertebral Disc Degeneration
Polymorphic variation of the guanosine triphosphate cyclohydrolase 1 gene predicts outcome in patients undergoing surgical treatment for lumbar degenerative disc disease.
Laryngeal Neoplasms
Polymorphic variants of folate metabolism genes and the risk of laryngeal cancer.
Leukemia
5-Aminoimidazole-4-carboxamide ribotide transformylase-IMP cyclohydrolase from human CCRF-CEM leukemia cells: purification, pH dependence, and inhibitors.
Leukemia
Targeting MTHFD2 in acute myeloid leukemia.
Leukemia, Myeloid, Acute
Targeting MTHFD2 in acute myeloid leukemia.
Leukemia, Myeloid, Acute
Upregulation of miR-504-3p is associated with favorable prognosis of acute myeloid leukemia and may serve as a tumor suppressor by targeting MTHFD2.
Liver Neoplasms
Correlation between methylation profile of promoter cpg islands of seven metastasis-associated genes and their expression states in six cell lines of liver origin.
Lung Neoplasms
Cancer stem-like properties and gefitinib resistance are dependent on purine synthetic metabolism mediated by the mitochondrial enzyme MTHFD2.
Lung Neoplasms
Down-regulation of MTHFD2 inhibits NSCLC progression by suppressing cycle-related genes.
Lung Neoplasms
Modulating redox homeostasis and cellular reprogramming through inhibited methylenetetrahydrofolate dehydrogenase 2 enzymatic activities in lung cancer.
Lymphatic Metastasis
Increased MTHFD2 expression is associated with poor prognosis in breast cancer.
Lymphoma, T-Cell
Therapeutic targeting of the mitochondrial one-carbon pathway: perspectives, pitfalls, and potential.
methenyltetrahydrofolate cyclohydrolase deficiency
GTP-cyclohydrolase deficiency responsive to sapropterin and 5-HTP supplementation: relief of treatment-refractory depression and suicidal behaviour.
methenyltetrahydrofolate cyclohydrolase deficiency
Mental retardation with hyperfolic-acidemia not associated with formiminoglutamic-acciduria: cyclohydrolase deficiency syndrome.
Migraine Disorders
Thymidylate synthase promoter tandem repeat and MTHFD1 R653Q polymorphisms modulate the risk for migraine conferred by the MTHFR T677 allele.
Musculoskeletal Pain
Epistasis between polymorphisms in COMT, ESR1, and GCH1 influences COMT enzyme activity and pain.
Myocardial Infarction
Empagliflozin improves post-infarction cardiac remodeling through GTP enzyme cyclohydrolase 1 and irrespective of diabetes status.
Neoplasm Metastasis
Increased MTHFD2 expression is associated with poor prognosis in breast cancer.
Neoplasm Metastasis
Methylenetetrahydrofolate dehydrogenase 2 overexpression is associated with tumor aggressiveness and poor prognosis in hepatocellular carcinoma.
Neoplasm Metastasis
Modulation of Redox Homeostasis by Inhibition of MTHFD2 in Colorectal Cancer: Mechanisms and Therapeutic Implications.
Neoplasm Metastasis
MTHFD2 promotes ovarian cancer growth and metastasis via activation of the STAT3 signaling pathway.
Neoplasm Metastasis
MTHFD2 promotes tumorigenesis and metastasis in lung adenocarcinoma by regulating AKT/GSK-3?/?-catenin signalling.
Neoplasm Metastasis
The effect of MTHFD2 on the proliferation and migration of colorectal cancer cell lines.
Neoplasm Metastasis
[The preliminary study on the function of methylenetetrahydrofolate dehydrogenase 2 in hepatocellular carcinoma].
Neoplasms
A Review of Small-Molecule Inhibitors of One-Carbon Enzymes: SHMT2 and MTHFD2 in the Spotlight.
Neoplasms
Author's reply to Kapoor S. GTP cyclohydrolase and cancer pain.
Neoplasms
Cancer stem-like properties and gefitinib resistance are dependent on purine synthetic metabolism mediated by the mitochondrial enzyme MTHFD2.
Neoplasms
Cisplatin inhibits SIRT3-deacetylation MTHFD2 to disturb cellular redox balance in colorectal cancer cell.
Neoplasms
Combinatorial targeting of MTHFD2 and PAICS in purine synthesis as a novel therapeutic strategy.
Neoplasms
Crystal Structure of the Emerging Cancer Target MTHFD2 in Complex with a Substrate-Based Inhibitor.
Neoplasms
Detection and characterisation of novel alternative splicing variants of the mitochondrial folate enzyme MTHFD2.
Neoplasms
Divergence in regulation of nitric-oxide synthase and its cofactor tetrahydrobiopterin by tumor necrosis factor-alpha. Ceramide potentiates nitric oxide synthesis without affecting GTP cyclohydrolase I activity.
Neoplasms
Drug discovery of anticancer drugs targeting methylenetetrahydrofolate dehydrogenase 2.
Neoplasms
Enhanced activation of NAD(P)H: quinone oxidoreductase 1 attenuates spontaneous hypertension by improvement of endothelial nitric oxide synthase coupling via tumor suppressor kinase liver kinase B1/adenosine 5'-monophosphate-activated protein kinase-mediated guanosine 5'-triphosphate cyclohydrolase 1 preservation.
Neoplasms
Folate-mediated one-carbon metabolism: a targeting strategy in cancer therapy.
Neoplasms
Glioma cells require one-carbon metabolism to survive glutamine starvation.
Neoplasms
High Expression of Methylenetetrahydrofolate Dehydrogenase 2 (MTHFD2) in Esophageal Squamous Cell Carcinoma and its Clinical Prognostic Significance.
Neoplasms
High-throughput RNAi screening for novel modulators of vimentin expression identifies MTHFD2 as a regulator of breast cancer cell migration and invasion.
Neoplasms
Identification of anaplastic lymphoma kinase variant translocations using 5'RACE.
Neoplasms
Increased MTHFD2 expression is associated with poor prognosis in breast cancer.
Neoplasms
Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer.
Neoplasms
Methylenetetrahydrofolate dehydrogenase 2 overexpression is associated with tumor aggressiveness and poor prognosis in hepatocellular carcinoma.
Neoplasms
MicroRNA-9 Inhibition of Cell Proliferation and Identification of Novel miR-9 Targets by Transcriptome Profiling in Breast Cancer Cells.
Neoplasms
miR-92a Inhibits Proliferation and Induces Apoptosis by Regulating Methylenetetrahydrofolate Dehydrogenase 2 (MTHFD2) Expression in Acute Myeloid Leukemia.
Neoplasms
Mitochondrial MTHFD isozymes display distinct expression, regulation, and association with cancer.
Neoplasms
Modulating redox homeostasis and cellular reprogramming through inhibited methylenetetrahydrofolate dehydrogenase 2 enzymatic activities in lung cancer.
Neoplasms
More Than a Metabolic Enzyme: MTHFD2 as a Novel Target for Anticancer Therapy?
Neoplasms
MTHFD2 Blockade Enhances the Efficacy of ?-Lapachone Chemotherapy With Ionizing Radiation in Head and Neck Squamous Cell Cancer.
Neoplasms
MTHFD2 facilitates breast cancer cell proliferation via the AKT signaling pathway.
Neoplasms
MTHFD2 links RNA methylation to metabolic reprogramming in renal cell carcinoma.
Neoplasms
MTHFD2 Overexpression Predicts Poor Prognosis in Renal Cell Carcinoma and is Associated with Cell Proliferation and Vimentin-Modulated Migration and Invasion.
Neoplasms
MTHFD2 promotes ovarian cancer growth and metastasis via activation of the STAT3 signaling pathway.
Neoplasms
NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase from ascites tumor cells. Purification and properties.
Neoplasms
p53 deficiency induces MTHFD2 transcription to promote cell proliferation and restrain DNA damage.
Neoplasms
Protein interaction and functional data indicate MTHFD2 involvement in RNA processing and translation.
Neoplasms
Quantitative proteomics study of breast cancer cell lines isolated from a single patient: discovery of TIMM17A as a marker for breast cancer.
Neoplasms
Somatic mutations in early onset luminal breast cancer.
Neoplasms
SOX7 Target Genes and Their Contribution to Its Tumor Suppressive Function.
Neoplasms
Stress-Mediated Reprogramming of Prostate Cancer One-Carbon Cycle Drives Disease Progression.
Neoplasms
Structure-Based Design and Synthesis of an Isozyme-Selective MTHFD2 Inhibitor with a Tricyclic Coumarin Scaffold.
Neoplasms
Suppression of MTHFD2 in MCF-7 Breast Cancer Cells Increases Glycolysis, Dependency on Exogenous Glycine, and Sensitivity to Folate Depletion.
Neoplasms
Systematic integration of molecular profiles identifies miR-22 as a regulator of lipid and folate metabolism in breast cancer cells.
Neoplasms
Targeting MTHFD2 in acute myeloid leukemia.
Neoplasms
The effect of MTHFD2 on the proliferation and migration of colorectal cancer cell lines.
Neoplasms
The folate cycle enzyme MTHFD2 induces cancer immune evasion through PD-L1 up-regulation.
Neoplasms
The folate-coupled enzyme MTHFD2 is a nuclear protein and promotes cell proliferation.
Neoplasms
The natural product carolacton inhibits folate-dependent C1 metabolism by targeting FolD/MTHFD.
Neoplasms
The one-carbon metabolism pathway highlights therapeutic targets for gastrointestinal cancer (Review).
Neoplasms
The Prognostic Significance of Immune-Related Metabolic Enzyme MTHFD2 in Head and Neck Squamous Cell Carcinoma.
Neoplasms
Therapeutic targeting of the mitochondrial one-carbon pathway: perspectives, pitfalls, and potential.
Neoplasms
Upregulation of miR-504-3p is associated with favorable prognosis of acute myeloid leukemia and may serve as a tumor suppressor by targeting MTHFD2.
Neoplasms
Xanthine Derivatives Reveal an Allosteric Binding Site in Methylenetetrahydrofolate Dehydrogenase 2 (MTHFD2).
Neoplasms
[The preliminary study on the function of methylenetetrahydrofolate dehydrogenase 2 in hepatocellular carcinoma].
Neoplasms, Squamous Cell
MTHFD2 Blockade Enhances the Efficacy of ?-Lapachone Chemotherapy With Ionizing Radiation in Head and Neck Squamous Cell Cancer.
Neural Tube Defects
A polymorphism, R653Q, in the trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase is a maternal genetic risk factor for neural tube defects: report of the Birth Defects Research Group.
Neuroblastoma
Combinatorial targeting of MTHFD2 and PAICS in purine synthesis as a novel therapeutic strategy.
Neuroblastoma
Effect of lipopolysaccharide on the gene expression of the enzymes involved in tetrahydrobiopterin de novo biosynthesis in murine neuroblastoma cell line N1E-115.
Neurologic Manifestations
Pediatric neurological syndromes and inborn errors of purine metabolism.
Ovarian Neoplasms
MTHFD2 promotes ovarian cancer growth and metastasis via activation of the STAT3 signaling pathway.
Pancreatic Neoplasms
The folate cycle enzyme MTHFD2 induces cancer immune evasion through PD-L1 up-regulation.
Parkinson Disease
Genetic diagnosis of two dopa-responsive dystonia families by exome sequencing.
Parkinsonian Disorders
Arg(184)His mutant GTP cyclohydrolase I, causing recessive hyperphenylalaninemia, is responsible for dopa-responsive dystonia with parkinsonism: a case report.
Parkinsonian Disorders
Genetic diagnosis of two dopa-responsive dystonia families by exome sequencing.
Phenylketonurias
Gene transfer of human guanosine 5'-triphosphate cyclohydrolase I restores vascular tetrahydrobiopterin level and endothelial function in low renin hypertension.
Phenylketonurias
Lessons from 30 years of selective screening for tetrahydrobiopterin deficiency.
Phenylketonurias
Proteasome-dependent degradation of guanosine 5'-triphosphate cyclohydrolase I causes tetrahydrobiopterin deficiency in diabetes mellitus.
Prostatic Neoplasms
Stress-Mediated Reprogramming of Prostate Cancer One-Carbon Cycle Drives Disease Progression.
Reperfusion Injury
Neuroprotective Effect of DAHP via Antiapoptosis in Cerebral Ischemia.
Severe Combined Immunodeficiency
Update and new concepts in vitamin responsive disorders of folate transport and metabolism.
Spinal Dysraphism
118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects.
Squamous Cell Carcinoma of Head and Neck
MTHFD2 Blockade Enhances the Efficacy of ?-Lapachone Chemotherapy With Ionizing Radiation in Head and Neck Squamous Cell Cancer.
Squamous Cell Carcinoma of Head and Neck
The Prognostic Significance of Immune-Related Metabolic Enzyme MTHFD2 in Head and Neck Squamous Cell Carcinoma.
Stomach Neoplasms
Effect of circ MTHFD2 on resistance to pemetrexed in gastric cancer through regulating expression of miR-124.
Stomach Neoplasms
MiR-22, regulated by MeCP2, suppresses gastric cancer cell proliferation by inducing a deficiency in endogenous S-adenosylmethionine.
Tuberculosis
Structural analyses of a purine biosynthetic enzyme from Mycobacterium tuberculosis reveal a novel bound nucleotide.
Tuberculosis
The crystal structure reveals the molecular mechanism of bifunctional 3,4-dihydroxy-2-butanone 4-phosphate synthase/GTP cyclohydrolase II (Rv1415) from Mycobacterium tuberculosis.
Whooping Cough
Comparative structural analysis of bifunctional methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase from Bordetella pertussis and Bordetella parapertussis: a drug target against pertussis.
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0.0164
(6R,S)-methenyltetrahydrofolate
-
-
0.016 - 0.043
10-formyltetrahydrofolate
0.05 - 2.36
5,10-methenyltetrahydrofolate
0.019 - 0.23
methenyltetrahydrofolate
additional information
additional information
-
0.016
10-formyltetrahydrofolate
-
reverse reaction, recombinant mutant S197D, substrate 10-formyltetrahydrofolate
0.018
10-formyltetrahydrofolate
-
reverse reaction, recombinant mutant R173K, substrate 10-formyltetrahydrofolate
0.02
10-formyltetrahydrofolate
-
reverse reaction, recombinant mutant S197T, substrate 10-formyltetrahydrofolate
0.024
10-formyltetrahydrofolate
-
reverse reaction, recombinant mutant R173A, substrate 10-formyltetrahydrofolate
0.026
10-formyltetrahydrofolate
-
reverse reaction, recombinant wild-type enzyme, substrate 10-formyltetrahydrofolate
0.028
10-formyltetrahydrofolate
-
reverse reaction, recombinant mutant S197R, substrate 10-formyltetrahydrofolate
0.031
10-formyltetrahydrofolate
-
reverse reaction, recombinant mutant R173E, substrate 10-formyltetrahydrofolate
0.043
10-formyltetrahydrofolate
-
reverse reaction, recombinant mutant S197A, substrate 10-formyltetrahydrofolate
0.05
5,10-methenyltetrahydrofolate
30°C, recombinant mutant R250A
0.06
5,10-methenyltetrahydrofolate
30°C, recombinant wild-type enzyme
0.071
5,10-methenyltetrahydrofolate
30°C, recombinant loop5G mutant
0.072
5,10-methenyltetrahydrofolate
30°C, recombinant mutant Y240A
0.077
5,10-methenyltetrahydrofolate
30°C, recombinant loop3G mutant
0.14
5,10-methenyltetrahydrofolate
mutant K56R
0.32
5,10-methenyltetrahydrofolate
mutant S49Q
0.34
5,10-methenyltetrahydrofolate
wild-type DC301
0.48
5,10-methenyltetrahydrofolate
mutant Y52F
0.52
5,10-methenyltetrahydrofolate
mutant S49A
0.56
5,10-methenyltetrahydrofolate
mutants C147A, T148A
1.22
5,10-methenyltetrahydrofolate
mutant Y52A
1.62
5,10-methenyltetrahydrofolate
mutant Y52F
2.36
5,10-methenyltetrahydrofolate
mutant C147Q
0.019
methenyltetrahydrofolate
-
forward reaction, recombinant mutant S197D
0.021
methenyltetrahydrofolate
-
forward reaction, recombinant mutant R173A and R173K
0.025
methenyltetrahydrofolate
-
forward reaction, recombinant mutant S197T
0.025
methenyltetrahydrofolate
-
forward reaction, recombinant wild-type enzyme
0.026
methenyltetrahydrofolate
-
forward reaction, recombinant mutant R173E
0.038
methenyltetrahydrofolate
-
forward reaction, recombinant mutant S197A
0.23
methenyltetrahydrofolate
-
forward reaction, recombinant mutant S197R
additional information
additional information
-
the His-tag does not alter the activity and kinetics of the enzymes
-
additional information
additional information
-
the overall forward reaction from mythylene- to formyltetrahydrofolate shows a hydride transfer kinetic isotope effect, whereas the the overall reverse reaction does not
-
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Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
113
recombinant mutant R250A, cyclohydrolase forward reaction
1173
-
forward reaction, recombinant mutant R173A, substrate 5,10-methenyltetrahydrofolate
12.8
-
reverse reaction, recombinant mutant R173K, substrate 10-formyltetrahydrofolate, in presence of 2',5'-ADP
13.5
-
forward reaction, recombinant mutant S197A, substrate 5,10-methenyltetrahydrofolate
15.9
-
reverse reaction, recombinant mutant S197T, substrate 10-formyltetrahydrofolate, in presence of 2',5'-ADP
161
recombinant wild-type enzyme, cyclohydrolase forward reaction
22.4
-
reverse reaction, recombinant wild-type enzyme, substrate 10-formyltetrahydrofolate, in presence of 2',5'-ADP
22.8
-
reverse reaction, recombinant mutant S197R, substrate 10-formyltetrahydrofolate, in presence of 2',5'-ADP
3.4
-
forward reaction, recombinant mutant S197R, substrate 5,10-methenyltetrahydrofolate
329
-
forward reaction, recombinant mutant R173K, substrate 5,10-methenyltetrahydrofolate
51
recombinant loop3G mutant, cyclohydrolase forward reaction
6.4
-
reverse reaction, recombinant mutant S197A, substrate 10-formyltetrahydrofolate, in absence of 2',5'-ADP
61.6
-
forward reaction, recombinant mutant S197D, substrate 5,10-methenyltetrahydrofolate
66.7
recombinant loop5G mutant, cyclohydrolase forward reaction
7.2
-
forward reaction, recombinant wild-type enzyme, substrate 5,10-methenyltetrahydrofolate
7.3
-
reverse reaction, recombinant mutant S197R, substrate 10-formyltetrahydrofolate, in absence of 2',5'-ADP
7.6
-
reverse reaction, recombinant mutant S197A, substrate 10-formyltetrahydrofolate, in presence of 2',5'-ADP
76.5
recombinant mutant Y240A, cyclohydrolase forward reaction
8
-
reverse reaction, recombinant mutant R173A, substrate 10-formyltetrahydrofolate, in presence of 2',5'-ADP
9
-
reverse reaction, recombinant mutant R173K, substrate 10-formyltetrahydrofolate, in absence of 2',5'-ADP
9.3
-
reverse reaction, recombinant mutant S197D, substrate 10-formyltetrahydrofolate, in absence of 2',5'-ADP
9.6
-
reverse reaction, recombinant wild-type enzyme, substrate 10-formyltetrahydrofolate, in absence of 2',5'-ADP
10.8
-
forward reaction, recombinant mutant S197T, substrate 5,10-methenyltetrahydrofolate
10.8
-
reverse reaction, recombinant mutant S197D, substrate 10-formyltetrahydrofolate, in presence of 2',5'-ADP
9.2
-
reverse reaction, recombinant mutant R173E, substrate 10-formyltetrahydrofolate, in presence of 2',5'-ADP
9.2
-
reverse reaction, recombinant mutant S197T, substrate 10-formyltetrahydrofolate, in absence of 2',5'-ADP
additional information
channeling efficiency of wild-type and mutant enzymes
additional information
-
channeling efficiency of wild-type and mutant enzymes
additional information
-
the His-tag does not alter the activity and kinetics of the enzymes, determination of methylenetetrahydrofolate dehydrogenase (NADP+), EC 1.5.1.5, activity, determination of forward channeling in percent
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D125A
site-directed mutagenesis, inactive mutant
D125C
site-directed mutagenesis, inactive mutant
D125E
site-directed mutagenesis, 95% reduced activity in the forward reaction compared to the wild-type enzyme
D125M
site-directed mutagenesis, inactive mutant
D125N
site-directed mutagenesis, inactive mutant
D125Q
site-directed mutagenesis, inactive mutant
Q100K
site-directed mutagenesis, inactive mutant
Q100M
site-directed mutagenesis, inactive mutant
Q100N
site-directed mutagenesis, inactive mutant
R173A
-
site-directed mutagenesis, at least 500fold increased Km for NADP+ compared to the wild-type, 163fold increased activity in the forward and reduced activity in the reverse reaction of the cyclohydrolase, unaltered channeling efficiency
R173E
-
site-directed mutagenesis, no dehydrogenase forward reaction activity, no forward channeling
R173K
-
site-directed mutagenesis, at least 500fold increased Km for NADP+ compared to the wild-type, 46fold increased activity in the forward and reduced activity in the reverse reaction of the cyclohydrolase, unaltered channeling efficiency
R250A
site-directed mutagenesis, 29.7% reduced activity in forward and reduced activity in the reverse reaction compared to the wild-type enzyme
S197A
-
site-directed mutagenesis, 20fold increased Km for NADP+ compared to the wild-type, reduced activity in the reverse reaction of the cyclohydrolase, no stimulation by 2',5'-ADP, unaltered channeling efficiency
S197D
-
site-directed mutagenesis, 8.5fold increased activity in the forward reaction of the cyclohydrolase, unaltered channeling efficiency
S197R
-
site-directed mutagenesis, 10fold increased Km for methenyltetrahydrofolate, reduced activity in the forward and reverse reaction of the cyclohydrolase, unaltered channeling efficiency
S197T
-
site-directed mutagenesis, slightly increased activity in the forward reaction of the cyclohydrolase, unaltered channeling efficiency
Y240A
site-directed mutagenesis, 52,5% reduced activity in forward and reduced activity in the reverse reaction compared to the wild-type enzyme
K56Q/Q100K
site-directed mutagenesis, mutant shows no cyclohydrolase activity, but retains more than 2 thirds of wild-type dehydrogenase activity
K56Q/Q100K
-
site-directed mutagenesis shows that the double mutant has no cyclohydrolase activity but retains two-thirds of the normal dehydrogenase activity
R653Q
-
geneotype analysis of 125 women, A1958A polymorphism, leading to amino acid exchange R653Q, in the MTHFD1 gene 1.64fold increases a mothers risk of having an unexplained second trimester pregnancy loss, overview
R653Q
mutant enzyme only affects the synthetase activity
additional information
construction of loop3G and loop5G deletion mutants which show 68.3% and 58.6% reduced activity, respectively, compared to the wild-type
additional information
-
construction of loop3G and loop5G deletion mutants which show 68.3% and 58.6% reduced activity, respectively, compared to the wild-type
additional information
-
MTHFD1 G1958A polymorphism/genotype occurs in spontaneous cervical artery dissections, methyleneterahydrofolate reductase and plasma homocysteine levels are also important, overview
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Saccharomyces cerevisiae, Homo sapiens, Sus scrofa
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Purification, crystallization, and preliminary X-ray studies of a bifunctional 5,10-methenyl/methylene tetrahydrofolate cyclohydrolase/dehydrogenase from Escherichia coli
Proteins
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Saccharomyces cerevisiae, Drosophila melanogaster, Escherichia coli, Homo sapiens, Rattus norvegicus, Escherichia coli BE
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Structures of three inhibitor complexes provide insight into the reaction mechanism of the human methylenetetrahydrofolate dehydrogenase/cyclohydrolase
Biochemistry
39
6325-6335
2000
Drosophila melanogaster, Mus musculus, Rattus norvegicus, Homo sapiens (P11586), Homo sapiens
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Pawelek, P.D.; MacKenzie, R.E.
Methenyltetrahydrofolate cyclohydrolase is rate limiting for the enzymatic conversion of 10-formyltetrahydrofolate to 5,10-methylenetetrahydrofolate in bifunctional dehydrogenase-cyclohydrolase enzymes
Biochemistry
37
1109-1115
1998
Homo sapiens, Mus musculus, Photobacterium phosphoreum, Saccharomyces cerevisiae, Sus scrofa
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Channeling efficiency in the bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase domain: the effects of site-directed mutagenesis of NADP binding residues
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1479
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Homo sapiens
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277
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Homo sapiens (P11586), Homo sapiens
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Konrad, C.; Mueller, G.A.; Langer, C.; Kuhlenbaeumer, G.; Berger, K.; Nabavi, D.G.; Dziewas, R.; Stoegbauer, F.; Ringelstein, E.B.; Junker, R.
Plasma homocysteine, MTHFR C677T, CBS 844ins68bp, and MTHFD1 G1958A polymorphisms in spontaneous cervical artery dissections
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A polymorphism in the MTHFD1 gene increases a mothers risk of having an unexplained second trimester pregnancy loss
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11
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2005
Homo sapiens
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Christensen, K.E.; Rohlicek, C.V.; Andelfinger, G.U.; Michaud, J.; Bigras, J.L.; Richter, A.; Mackenzie, R.E.; Rozen, R.
The MTHFD1 p.Arg653Gln variant alters enzyme function and increases risk for congenital heart defects
Hum. Mutat.
30
212-220
2009
Homo sapiens (P11586)
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Mitochondrial methylenetetrahydrofolate dehydrogenase, methenyltetrahydrofolate cyclohydrolase, and formyltetrahydrofolate synthetases
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79
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Polymorphic variants of folate metabolism genes and the risk of laryngeal cancer
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Human mitochondrial MTHFD2 is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase
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5
11
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Homo sapiens (P13995), Homo sapiens (Q9H903), Homo sapiens
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9
2292
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