EC Number   |
General Information |
Reference |
|---|
    6.3.4.3 | evolution |
one-carbon metabolic pathway rewiring in Escherichia coli reveals an evolutionary advantage of 10-formyltetrahydrofolate synthetase in survival under hypoxia |
-, 742789 |
| 6.3.4.3 | malfunction |
complete loss of synthetase activity is incompatible with life. Embryos die shortly after 10.5 days gestation, and are developmentally delayed or abnormal. Female synthetase-deficient mice have decreased neutrophil counts during pregnancy and increased incidence of developmental defects in embryos. Synthetase deficiency may lead to pregnancy complications through decreased purine synthesis and reduced cellular proliferation |
727607 |
| 6.3.4.3 | malfunction |
knockdown of MTHFD1L impedes hepatocellular carcinoma (HCC) proliferation through induction of oxidative stress and ROS-associated cell cycle delay. In the MTHFD1L-knockdown HCC cells, the levels of TCA cycle metabolic intermediates derived from pyruvate/acetyl-CoA, including citrate, cis-aconitate, and isocitrate, decrease |
765141 |
| 6.3.4.3 | malfunction |
knockdown of MTHFD1L suppresses cell proliferation, colony formation, and tumorigenesis, while it induces apoptosis in oral squamous cell carcinoma (OSCC). Mechanistically, a microarray analysis shows that MTHFD1L suppresses c-MYC and activates p53 signaling by regulating the protein expression of TP53, GADD45A, FAS and JUN. the suppression of MTHFD1L affects c-MYC expression and thereby inhibits tumor cell proliferation and induces apoptosis. MTHFD1L knockdown may affect JUN expression through MAGED and induce cell apoptosis of the tumor. |
765861 |
| 6.3.4.3 | malfunction |
the elevation of oxidative stress through MTHFD1L knockdown or the use of methotrexate, an antifolate drug, sensitizes cancer cells to sorafenib, a targeted therapy for hepatocellular carcinoma |
765141 |
| 6.3.4.3 | metabolism |
FTHFS is a key enzyme of the Wood-Ljungdahl pathway |
701825 |
| 6.3.4.3 | metabolism |
most organisms possess bifunctional FolD [5,10-methylenetetrahydrofolate (5,10-CH2-THF) dehydrogenase-cyclohydrolase] to generate NADPH and 10-formyltetrahdrofolate (10-CHO-THF) required in various metabolic steps. In addition, some organisms including Clostridium perfringens possess another protein, Fhs (formyltetrahydrofolate synthetase), to synthesize 10-CHO-THF. The presence of the three clostridial proteins, monofunctional 5,10-methenyltetrahydrofolate dehydrogenase FolD, 5,10-methenyltetrahydrofolate cyclohydrolase FchA, and 10-formyltetrahdrofolate synthetase Fhs, is required to maintain folate homeostasis in the cell, overview |
-, 743250 |
| 6.3.4.3 | metabolism |
the enzyme plays a central role in folate homeostasis and serve as targets for antibacterials |
-, 743250 |
| 6.3.4.3 | metabolism |
the folate cycle is an important metabolic pathway that fulfills a number of cancer-specific nutrient demands. Folate (folic acid), or vitamin B9, is commonly found in Western diets and dietary supplements. A 1-carbon (1C) unit from serine is transferred to tetrahydrofolate (THF) by serine hydroxymethyl transferases (SHMTs) to form 5,10-methylenetetrahydrofolate (CH2-THF). The 1C unit is then transferred from one position of THF to another, thus creating the folate cycle. The folate cycle is composed of the cytoplasmic and mitochondrial compartments. The cytoplasmic compartment is carried out by methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 (MTHFD1), while the mitochondrial compartment is carried out by MTHFD2/2L and methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L). MTHFD1 is a cytoplasmic trifunctional enzyme with CH2-THF dehydrogenase (EC 1.5.1.5), 5,10-methenyl-tetrahydrofolate (CH+-THF, EC 3.5.4.9) cyclohydrolase, and 10-formyl-tetrahydrofolate (10-CHO-THF, EC 6.3.4.3) synthase activities |
765141 |
| 6.3.4.3 | physiological function |
expression of Clostridium perfringens Fhs and FolD-FchA rescue the photosensitive phenotype of an Escherichia coli DELTAGlyA strain |
743250 |
