monofunctional C1-tetrahydrofolate synthase, mitochondrial (formyltetrahydrofolate synthetase, MTHFD1L, FTHFSDC1)
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Function
- may provide missing metabolic reaction required to link the mitochondria & the cytoplasm in mammalian model of one-carbon folate metabolism in embryonic & transformed cells complementing enzymatic activities of MTHFD2
- one-carbon metabolism; tetrahydrofolate pathway
ATP + formate + tetrahydrofolate
<-->
ADP + phosphate + 10-formyltetrahydrofolate
Kinetic parameters: KM=500 uM for THF monoglutamate KM=16 uM for THF triglutamate KM=3.6 uM for THF pentaglutamate
Structure
- homodimer
- two major domains:
- N-terminal inactive methylene-THF dehydrogenase & cyclohydrolase domain
- active larger formyl-THF synthetase C-terminal domain
- tetrahydrofolate dehydrogenase/cyclohydrolase family tetrahydrofolate ligase family
Compartment
Alternative splicing
named isoforms=2
Expression
- detected in most tissues
- highest expression found in placenta, thymus & brain
- low expression in liver & skeletal muscle
Pathology
- up-regulated in colon adenocarcinoma
- may participate in the progression of colorectal cancer by conferring growth advantage
- polymorphism associated with late onset Alzheimer's disease ?[2]
Notes
- lacks methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) & ethenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9) activities
- an enzyme performing these two complementary activities has not been found in adult mitochondrial tissues
- MTHFD2, which performs these two activities, is found in developing tissues only