|Superclasses:||Reactions Classified By Conversion Type → Simple Reactions → Chemical Reactions|
|Reactions Classified By Substrate → Small-Molecule Reactions|
EC Number: 220.127.116.11
Enzymes and Genes:
|Arabidopsis thaliana col:||folylpolyglutamate synthetase: DHFS/FPGS3|
folylpolyglutamate synthetase: DHFS/FPGS2
folylpolyglutamate synthetase: DHFS/FPGS4
|Corynebacterium sp.:||tetrahydrofolate synthase: folC|
|Escherichia coli K-12 substr. MG1655:||bifunctional folylpolyglutamate synthetase / dihydrofolate synthetase: folC|
|Homo sapiens:||folylpolyglutamate synthase: FPGS|
|Lactobacillus casei:||tetrahydrofolate synthase: folC|
In Pathway: folate polyglutamylation
Note that this reaction equation differs from the official Enzyme Commission reaction equation for this EC number, which can be found here .
The direction shown, i.e. which substrates are on the left and right sides, is in accordance with the direction in which it was curated.
Mass balance status: Marked as unbalanced.
Enzyme Commission Primary Name: tetrahydrofolate synthase
Enzyme Commission Synonyms: folylpolyglutamate synthase, folate polyglutamate synthetase, formyltetrahydropteroyldiglutamate synthetase, N10-formyltetrahydropteroyldiglutamate synthetase, folylpoly-γ-glutamate synthase, folylpolyglutamyl synthetase, folylpoly(γ-glutamate) synthase, folylpolyglutamate synthetase, folylpoly-γ-glutamate synthetase-dihydrofolate synthetase, FPGS, tetrahydrofolylpolyglutamate synthase, tetrahydrofolate:L-glutamate γ-ligase (ADP-forming), tetrahydropteroyl-[γ-Glu]n:L-glutamate γ-ligase (ADP-forming)
Standard Gibbs Free Energy (ΔrG'° in kcal/mol): 38.100403 [Latendresse13]
Enzyme Commission Summary:
In some bacteria, a single protein catalyses both this activity and that of EC 18.104.22.168, dihydrofolate synthase [Bognar85], the combined activity of which leads to the formation of the coenzyme polyglutamated tetrahydropteroate (H4PteGlun), i.e. various tetrahydrofolates (H4folate). In contrast, the activities are located on separate proteins in most eukaryotes studied to date [Ravanel01]. In Arabidopsis thaliana col, this enzyme is present as distinct isoforms in the mitochondria, the cytosol and the chloroplast. Each isoform is encoded by a separate gene, a situation that is unique among eukaryotes [Ravanel01]. As the affinity of folate-dependent enzymes increases markedly with the number of glutamic residues, the tetrahydropteroyl polyglutamates are the preferred coenzymes of C1 metabolism. (reviewed in [Cossins97]). The enzymes from different sources (particularly eukaryotes versus prokaryotes) have different substrate specificities with regard to one-carbon substituents and the number of glutamate residues present on the tetrahydrofolates.
Instance reactions of [tetrahydropteroyl-[γ-Glu](n) + L-glutamate + ATP → tetrahydropteroyl-[γ-Glu](n+1) + ADP + phosphate] (22.214.171.124):
i1: 10-formyl-tetrahydropteroyl-[γ-Glu](n) + L-glutamate + ATP → 10-formyl-tetrahydropteroyl-[γ-Glu](n+1) + ADP + phosphate (126.96.36.199)
i2: methylene-tetrahydropteroyl-[γ-Glu](n) + L-glutamate + ATP → methylene-tetrahydropteroyl-[γ-Glu](n+1) + ADP + phosphate (188.8.131.52)
i3: an (6S)-N5-formyl-tetrahydrofolate + L-glutamate + ATP = 5-formyl-THF-Glun+1 + ADP + phosphate (no EC#)
Bognar85: Bognar AL, Osborne C, Shane B, Singer SC, Ferone R (1985). "Folylpoly-gamma-glutamate synthetase-dihydrofolate synthetase. Cloning and high expression of the Escherichia coli folC gene and purification and properties of the gene product." J Biol Chem 1985;260(9);5625-30. PMID: 2985605
Cherest00: Cherest H, Thomas D, Surdin-Kerjan Y (2000). "Polyglutamylation of folate coenzymes is necessary for methionine biosynthesis and maintenance of intact mitochondrial genome in Saccharomyces cerevisiae." J Biol Chem 275(19);14056-63. PMID: 10799479
Ravanel01: Ravanel S, Cherest H, Jabrin S, Grunwald D, Surdin-Kerjan Y, Douce R, Rebeille F (2001). "Tetrahydrofolate biosynthesis in plants: molecular and functional characterization of dihydrofolate synthetase and three isoforms of folylpolyglutamate synthetase in Arabidopsis thaliana." Proc Natl Acad Sci U S A 98(26);15360-5. PMID: 11752472
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