Any feedback?
Literature summary for 3.5.4.9 extracted from
- Mitochondrial methylenetetrahydrofolate dehydrogenase, methenyltetrahydrofolate cyclohydrolase, and formyltetrahydrofolate synthetases (2008), Vitam. Horm., 79, 393-410.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| 2',5'-ADP | analog of NADP+ does not stimulate the reverse cyclohydrolase activity | Homo sapiens |  |
| 2',5'-ADP | the analog of NADP+ stimulates the reverse cyclohydrolase activity by more than 2fold | Homo sapiens | |
| 5'-ADP | analog of NADP+ does not stimulate the reverse cyclohydrolase activity | Homo sapiens | |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| deletion of the MIS1 gene has little effect | Saccharomyces cerevisiae |
| null mutation is embryonic lethal at about 12 days gestation, knockout of enzyme establishes the important role of formate production during embryogenesis | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| K56Q/Q100K | site-directed mutagenesis shows that the double mutant has no cyclohydrolase activity but retains two-thirds of the normal dehydrogenase activity | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| NADP+ | - |
Homo sapiens | |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 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 | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytoplasm | - |
Homo sapiens | 5737 | - |
| cytosol | - |
Saccharomyces cerevisiae | 5829 | - |
| mitochondrion | - |
Homo sapiens | 5739 | - |
| mitochondrion | - |
Saccharomyces cerevisiae | 5739 | - |
Molecular Weight [Da]
| Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|
| 34000 | - |
MTHFD2 evolves from a trifunctional dehydrogenase-cyclohydrolase-synthetase precursor with the loss of synthetase function | Homo sapiens |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 5,10-methenyl-tetrahydrofolate + H2O | Saccharomyces cerevisiae | trifunctional enzyme exhibits synthetase, dehydrogenase and cyclohydrolase activities | 10-formyltetrahydrofolate + H+ | - |
r | |
| 5,10-methenyltetrahydrofolate + H2O | Homo sapiens | bifunctional enzyme exhibits dihydrogenase and cyclohydrolase activities | 10-formyltetrahydrofolate | - |
r | |
| 5,10-methenyltetrahydrofolate + H2O | Homo sapiens | trifunctional enzyme exhibits synthetase, dehydrogenase and cyclohydrolase activities | 10-formyltetrahydrofolate | - |
r | |
| additional information | Homo sapiens | the conversion of formyl- to methylenehydrofolate is rate-limited by the slow conversion by the cyclohydrolase of formyl- to methenyltetrahydrofolate | ? | - |
? | |
| additional information | Saccharomyces cerevisiae | the presence of cytoplasmic and mitochondrial isoforms of a trifunctional dehydrogenase-cyclohydrolase-synthetase support a model wherin the mitochondria can produce fromate which can be used by the cytoplasmic enzymes for the synthesis of purins and for methylation reactions | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
| Homo sapiens | - |
enzyme is unique in mammals | - |
| Saccharomyces cerevisiae | P07245 | - |
- |
| Saccharomyces cerevisiae | P09440 | - |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| ascites tumor cell | - |
Homo sapiens | - |
| additional information | the cytoplasmic MTHFD1 is ubiquitously expressed in all mammalian cells | Homo sapiens | - |
| additional information | the mitochondrial MTHFD2 is detected only in transformed cell lines and embryogenic tissues | Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 5,10-methenyl-tetrahydrofolate + H2O | trifunctional enzyme exhibits synthetase, dehydrogenase and cyclohydrolase activities | Saccharomyces cerevisiae | 10-formyltetrahydrofolate + H+ | - |
r | |
| 5,10-methenyltetrahydrofolate + H2O | bifunctional enzyme exhibits dihydrogenase and cyclohydrolase activities | Homo sapiens | 10-formyltetrahydrofolate | - |
r | |
| 5,10-methenyltetrahydrofolate + H2O | trifunctional enzyme exhibits synthetase, dehydrogenase and cyclohydrolase activities | Homo sapiens | 10-formyltetrahydrofolate | - |
r | |
| additional information | the conversion of formyl- to methylenehydrofolate is rate-limited by the slow conversion by the cyclohydrolase of formyl- to methenyltetrahydrofolate | Homo sapiens | ? | - |
? | |
| additional information | the presence of cytoplasmic and mitochondrial isoforms of a trifunctional dehydrogenase-cyclohydrolase-synthetase support a model wherin the mitochondria can produce fromate which can be used by the cytoplasmic enzymes for the synthesis of purins and for methylation reactions | Saccharomyces cerevisiae | ? | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| ADE3 | - |
Saccharomyces cerevisiae |
| dehydrogenasse-cyclohydrolase-synthetase | - |
Saccharomyces cerevisiae |
| methenyltetrahydrofolate cyclohydrolase | - |
Homo sapiens |
| methenyltetrahydrofolate cyclohydrolase | - |
Saccharomyces cerevisiae |
| MIS1 | - |
Saccharomyces cerevisiae |
| MTHFD1 | - |
Homo sapiens |
| MTHFD2 | - |
Homo sapiens |
| NAD-dependent methylenetetrahydrofolate dehydrogenase-cyclohydrolase | - |
Homo sapiens |
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
