C-1-tetrahydrofolate synthase, cytoplasmic

Definition:

Trifunctional enzyme that catalyzes the interconversion of three forms of one-carbon-substituted tetrahydrofolate: (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate, 5,10-methenyltetrahydrofolate and (6S)-10-formyltetrahydrofolate. These derivatives of tetrahydrofolate are differentially required in nucleotide and amino acid biosynthesis, (6S)-10-formyltetrahydrofolate being required for purine biosynthesis while (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate is used for serine and methionine biosynthesis for instance.

References:

[1]. D W Hum, et al. Expression of active domains of a human folate-dependent trifunctional enzyme in Escherichia coli. Protein Eng. 1991 Apr;4(4):493-500. [Content Brief]

[2]. Karen E Christensen, et al. The MTHFD1 p.Arg653Gln variant alters enzyme function and increases risk for congenital heart defects. Hum Mutat. 2009 Feb;30(2):212-20. [Content Brief]

[3]. P Burda, et al. Characterization and review of MTHFD1 deficiency: four new patients, cellular delineation and response to folic and folinic acid treatment. J Inherit Metab Dis. 2015 Sep;38(5):863-72. [Content Brief]

[4]. A Schmidt, et al. Structures of three inhibitor complexes provide insight into the reaction mechanism of the human methylenetetrahydrofolate dehydrogenase/cyclohydrolase. Biochemistry. 2000 May 30;39(21):6325-35. [Content Brief]

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