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Literature summary for 6.3.4.3 extracted from
- Mitochondrial methylenetetrahydrofolate dehydrogenase, methenyltetrahydrofolate cyclohydrolase, and formyltetrahydrofolate synthetases (2008), Vitam. Horm., 79, 393-410.
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| deletion of the MIS1 gene has little effect | Saccharomyces cerevisiae |
| expressed in Escherichia coli | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytoplasm | - |
Homo sapiens | 5737 | - |
| cytosol | ADE3 | Saccharomyces cerevisiae | 5829 | - |
| mitochondrion | - |
Homo sapiens | 5739 | - |
| mitochondrion | - |
Saccharomyces cerevisiae | 5739 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 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 | ? | - |
? |  |
| tetrahydrofolate + formate + ATP | Homo sapiens | monofunctional enzyme similar in structure to the cytoplasmatic trifunctional enzyme, dehydrogenase and cyclohydrolase activities are silent due to mutations of critical binding and catalytic residues | 10-formyltetrahydrofolate + ADP + phosphate | mitochondria also use formyltetrahydrofolate to produce formylmethionyl-tRNA to initiate protein synthesis | r | |
| tetrahydrofolate + formate + ATP | Homo sapiens | trifunctional enzyme exhibits synthetase, dehydrogenase and cyclohydrogenase activities | 10-formyltetrahydrofolate + ADP + phosphate | - |
r | |
| tetrahydrofolate + formate + ATP | Saccharomyces cerevisiae | trifunctional enzyme exhibits synthetase, dehydrogenase and cyclohydrolase activities | 10-formyltetrahydrofolate + ADP + phosphate | - |
r | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
| Saccharomyces cerevisiae | P07245 | - |
- |
| Saccharomyces cerevisiae | P09440 | - |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| adenocarcinoma cell | - |
Homo sapiens | - |
| brain | - |
Homo sapiens | - |
| HEK-293 cell | - |
Homo sapiens | - |
| leukocyte | low expression | Homo sapiens | - |
| lung | - |
Homo sapiens | - |
| lymphocyte | low expression | Homo sapiens | - |
| additional information | the cytoplasmatic MTHFD1 is ubiquitously expressed in all mammalian cells | Homo sapiens | - |
| muscle | low expression | Homo sapiens | - |
| ovary | - |
Homo sapiens | - |
| placenta | - |
Homo sapiens | - |
| spleen | - |
Homo sapiens | - |
| thymus | - |
Homo sapiens | - |
Specific Activity [micromol/min/mg]
| Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
|---|---|---|---|
| additional information | - |
MTHFD1L is upregulated in colon adeno-carcinomas | Homo sapiens |
| additional information | - |
overexpression of MTHFD1L in HEK-292 cells stimulates colony formation indicating that expression of this gene confers a growth advantage | Homo sapiens |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 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 | ? | - |
? | |
| tetrahydrofolate + formate + ATP | monofunctional enzyme similar in structure to the cytoplasmatic trifunctional enzyme, dehydrogenase and cyclohydrolase activities are silent due to mutations of critical binding and catalytic residues | Homo sapiens | 10-formyltetrahydrofolate + ADP + phosphate | mitochondria also use formyltetrahydrofolate to produce formylmethionyl-tRNA to initiate protein synthesis | r | |
| tetrahydrofolate + formate + ATP | trifunctional enzyme exhibits synthetase, dehydrogenase and cyclohydrogenase activities | Homo sapiens | 10-formyltetrahydrofolate + ADP + phosphate | - |
r | |
| tetrahydrofolate + formate + ATP | trifunctional enzyme exhibits synthetase, dehydrogenase and cyclohydrolase activities | Saccharomyces cerevisiae | 10-formyltetrahydrofolate + ADP + phosphate | - |
r | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| dimer | by gel filtration | Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| 10-Formyltetrahydrofolate synthetase | - |
Homo sapiens |
| ADE3 | - |
Saccharomyces cerevisiae |
| dehydrogenasse-cyclohydrolase-synthetase | - |
Saccharomyces cerevisiae |
| Formyltetrahydrofolate synthetase | - |
Homo sapiens |
| Formyltetrahydrofolate synthetase | - |
Saccharomyces cerevisiae |
| MIS1 | - |
Saccharomyces cerevisiae |
| MTHFD1 | - |
Homo sapiens |
| MTHFD1L | - |
Homo sapiens |
Turnover Number [1/s]
| Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | the Kcat/Km tetrahydrofolate values are 0.03 s/M for the monoglutamate and 0.71 s/M for the pentaglutatmate substrates | Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | - |
Homo sapiens | |
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