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MTHFD1 is a gene located in humans on chromosome 14 that encodes for a protein with three distinct enzymatic activities. C-1-tetrahydrofolate synthase, cytoplasmic also known as C1-THF synthase is an enzyme that in humans is encoded by the ''MTHFD1'' (methylenetetrahydrofolate dehydrogenase 1) gene.


Function

This gene encodes a protein that possesses three distinct enzymatic activities, methylenetetrahydrofolate dehydrogenase (1.5.1.5), methenyltetrahydrofolate cyclohydrolase (3.5.4.9) and
formate–tetrahydrofolate ligase In enzymology, a formate—tetrahydrofolate ligase () is an enzyme that catalyzes the chemical reaction :ATP + formate + tetrahydrofolate \rightleftharpoons ADP + phosphate + 10-formyltetrahydrofolate The 3 substrates of this enzyme are ATP, ...
(6.3.4.3). Each of these activities catalyzes one of three sequential reactions in the interconversion of 1-carbon derivatives of tetrahydrofolate, which are substrates for
methionine Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical ro ...
, thymidylate, and de novo purine syntheses. The trifunctional enzymatic activities are conferred by two major domains, an aminoterminal portion containing the dehydrogenase and cyclohydrolase activities and a larger synthetase domain.


Clinical significance

Mutations of the MTHFD1 gene may cause methylenetetrahydrofolate dehydrogenase 1 deficiency, also known as combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia (CIMAH).


References


Further reading

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External links

* EC 6.3.4 {{gene-14-stub