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MetaCyc Enzyme: tetrahydrofolate synthase

Gene: folC Accession Number: G-3701 (MetaCyc)

Synonyms: folylpoly-γ-glutamate synthetase

Species: Lactobacillus casei

Summary:
The Lactobacillus casei folylpoly-γ-glutamate synthetase has about 33% overall amino acid identity with the Escherichia coli enzyme. Unlike the Escherichia coli enzyme it lacks dihydrofolate synthetase activity [Toy90].

Molecular Weight of Polypeptide: 43.0 kD (from nucleotide sequence)

Relationship Links: Entrez-Nucleotide:PART-OF:J05221

Gene-Reaction Schematic: ?

MultiFun Terms: metabolism biosynthesis of building blocks cofactors, small molecule carriers folic acid


Enzymatic reaction of: tetrahydropteroyl-γ-polyglutamate:L-glutamate γ-ligase (ADP-forming) (tetrahydrofolate synthase)

EC Number: 6.3.2.17

tetrahydropteroyl-[γ-Glu](n) + L-glutamate + ATP <=> tetrahydropteroyl-[γ-Glu](n+1) + ADP + phosphate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown.

In Pathways: folate polyglutamylation

Summary:
5,10-methylene-PteGlun derivatives were the preferred pteroylmono- and polyglutamate substrates for this enzyme, although some activity was observed with PteGlun derivatives [Bognar83].


Enzymatic reaction of: 5,10-methylene-tetrahydrofolate:L-glutamate γ-ligase (ADP-forming) (tetrahydrofolate synthase)

EC Number: 6.3.2.17

methylene-tetrahydropteroyl-[γ-Glu](n) + L-glutamate + ATP <=> methylene-tetrahydropteroyl-[γ-Glu](n+1) + ADP + phosphate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

Alternative Substrates for ATP: GTP [Bognar83 ] , ITP [Bognar83 ] , UTP [Bognar83 ]

Alternative Substrates for L-glutamate: L-homocysteate [Bognar83 ] , 4- fluoroglutamate [Bognar83 ]

Alternative Products for ADP: dATP [Bognar83 ]

Alternative Products for a 5,10-methylene-tetrahydrofolate: a tetrahydrofolate [Bognar83 ] , an N10-formyl-tetrahydrofolate [Bognar83 ]

In Pathways: folate polyglutamylation

Summary:
The purified enzyme catalyzed a MgATP-dependent addition of glutamate to 5,10-methylene-tetrahydropteroylmono-, di-, and triglutamate substrates, and metabolized 5,10-methylene-tetrahydrofolate to the tetraglutamate derivative.

The magnesium salts of dATP, GTP, ITP, and UTP were effective alternate substrates for MgATP. The specificity of the glutamate binding site was very narrow. Of a wide variety of analogs tested, only L-homocysteate and 4- fluoroglutamate demonstrated affinity for the enzyme [Bognar83].

5,10-methylene-PteGlun derivatives were the preferred pteroylmono- and polyglutamate substrates H4PteGlu, and 10-formyl-H4PteGlu, were less effective substrates or lacked activity. With each 1-carbon folate form, the diglutamate was the most effective substrate. Only low levels of activity were observed with derivatives of glutamate chain length four and above [Bognar83].

Kinetic Parameters:

Substrate
Km (μM)
Citations
L-glutamate
423.0
[Bognar83]
ATP
5600.0
[Bognar83]
a 5,10-methylene-tetrahydrofolate
2.3
[Bognar83]


Enzymatic reaction of: N10-formyl-tetrahydrofolate:L-glutamate γ-ligase (ADP-forming) (tetrahydrofolate synthase)

EC Number: 6.3.2.17

10-formyl-tetrahydropteroyl-[γ-Glu](n) + L-glutamate + ATP <=> 10-formyl-tetrahydropteroyl-[γ-Glu](n+1) + ADP + phosphate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

In Pathways: folate polyglutamylation

Summary:
5,10-methylene-PteGlun derivatives were the preferred pteroylmono- and polyglutamate substrates for this enzyme, although some activity was observed with 10-formyl-PteGlun derivatives [Bognar83].


References

Bognar83: Bognar AL, Shane B (1983). "Purification and properties of Lactobacillus casei folylpoly-gamma-glutamate synthetase." J Biol Chem 258(20);12574-81. PMID: 6138353

Toy90: Toy J, Bognar AL (1990). "Cloning and expression of the gene encoding Lactobacillus casei folylpoly-gamma-glutamate synthetase in Escherichia coli and determination of its primary structure." J Biol Chem 265(5);2492-9. PMID: 2105929


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Wed Dec 17, 2014, biocyc13.