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MetaCyc Compound: tetrahydropteroyl mono-L-glutamate

Synonyms: H4PteGlu, 5,6,7,8-tetrahydrofolic acid, tetrahydrofolic acid, (6S)-tetrahydrofolate, H4PteGlu1, tetrahydrofolate, tetrahydrafolate, 5,6,7,8-tetrahydrofolate, THF, tetra-H-folate, th-folate, FH4, folate-H4, tetrahydropteroylglutamate, H4F, vitamin B9

Superclasses: a cofactor a prosthetic group a folate a tetrahydrofolate
a vitamin a folate a tetrahydrofolate
an organic heterocyclic compound an organic heterobicyclic compound a pteridine a pterin a pteroate a folate a tetrahydrofolate
an organic heterocyclic compound an organonitrogen heterocyclic compound a pteridine a pterin a pteroate a folate a tetrahydrofolate

Summary:
Tetrahydrofolate (vitamin B9) and its derivatives, commonly termed folates, are essential cofactors that facilitate the transfer of one-carbon units from donor molecules into important biosynthetic pathways leading to methionine, purine, and pyrimidine biosynthesis. Folates also mediate the interconversion of serine and glycine, play a role in histidine catabolism [Lucock00], and in plants are also involved in photorespiration, amino acid metabolism and chloroplastic protein biosynthesis [Hanson02] [Jabrin03].

Chemical Formula: C19H21N7O6

Molecular Weight: 443.42 Daltons

Monoisotopic Molecular Weight: 445.1709815073 Daltons

SMILES: C(NC1(C=CC(C(=O)NC(C(=O)[O-])CCC([O-])=O)=CC=1))[CH]3(CNC2(=C(C(=O)NC(N)=N2)N3))

InChI: InChI=1S/C19H23N7O6/c20-19-25-15-14(17(30)26-19)23-11(8-22-15)7-21-10-3-1-9(2-4-10)16(29)24-12(18(31)32)5-6-13(27)28/h1-4,11-12,21,23H,5-8H2,(H,24,29)(H,27,28)(H,31,32)(H4,20,22,25,26,30)/p-2/t11-,12-/m0/s1

InChIKey: InChIKey=MSTNYGQPCMXVAQ-RYUDHWBXSA-L

Unification Links: CAS:135-16-0 , CAS:29347-89-5 , ChEBI:57453 , HMDB:HMDB01846 , IAF1260:33856 , KEGG:C00101 , MetaboLights:MTBLC57453 , PubChem:25790919

Standard Gibbs Free Energy of Change Formation (ΔfG in kcal/mol): 73.9153 Inferred by computational analysis [Latendresse13]

Reactions known to consume the compound:

dimethylsulfoniopropionate degradation III (demethylation) :
3-(methylthio)propanoate + an N5-methyl-tetrahydrofolate + H+ ← dimethylsulfoniopropanoate + a tetrahydrofolate

folate polyglutamylation :
a tetrahydrofolate + ATP + formate → 10-formyl-tetrahydropteroyl-[γ-Glu](n) + ADP + phosphate
tetrahydropteroyl-[γ-Glu](n) + L-glutamate + ATP → tetrahydropteroyl-[γ-Glu](n+1) + ADP + phosphate

folate transformations I , folate transformations II , formate reduction to 5,10-methylenetetrahydrofolate , reductive acetyl coenzyme A pathway :
a tetrahydrofolate + ATP + formate → 10-formyl-tetrahydropteroyl-[γ-Glu](n) + ADP + phosphate

formaldehyde assimilation I (serine pathway) :
formaldehyde + a tetrahydrofolate → a 5,10-methylene-tetrahydrofolate + H2O

glutamate removal from folates :
tetrahydropteroyl-[γ-Glu](n) + H2O → tetrahydropteroyl-[γ-Glu](n-1) + L-glutamate

glycine betaine degradation II (mammalian) :
sarcosine + an oxidized electron-transfer flavoprotein + a tetrahydrofolate → glycine + a 5,10-methenyltetrahydrofolate + a reduced electron-transfer flavoprotein
dimethylglycine + an oxidized electron-transfer flavoprotein + a tetrahydrofolate → sarcosine + a 5,10-methenyltetrahydrofolate + a reduced electron-transfer flavoprotein

histidine degradation III :
a 5-formiminotetrahydrofolate + L-glutamate ← N-formimino-L-glutamate + a tetrahydrofolate

syringate degradation :
3-O-methylgallate + a tetrahydrofolate → gallate + an N5-methyl-tetrahydrofolate
syringate + a tetrahydrofolate → 3-O-methylgallate + an N5-methyl-tetrahydrofolate

vanillin and vanillate degradation I :
vanillate + a tetrahydrofolate → protocatechuate + an N5-methyl-tetrahydrofolate

Reactions known to produce the compound:

folate transformations I :
a tetrahydrofolate + trimethyl sulfonium ← dimethyl sulfide + an N5-methyl-tetrahydrofolate + H+
an N10-formyl-tetrahydrofolate + H2O → a tetrahydrofolate + formate + H+
L-homocysteine + an N5-methyl-tetrahydrofolate → L-methionine + a tetrahydrofolate

folate transformations II :
a tetrahydrofolate + NADP+ ← a 7,8-dihydrofolate + NADPH + H+
L-homocysteine + an N5-methyl-tetrahydrofolate → L-methionine + a tetrahydrofolate

methionine biosynthesis I , methionine biosynthesis III , methionine salvage from homocysteine :
L-homocysteine + an N5-methyl-tetrahydrofolate → L-methionine + a tetrahydrofolate

N10-formyl-tetrahydrofolate biosynthesis :
a tetrahydrofolate + NADP+ ← a 7,8-dihydrofolate + NADPH + H+
L-homocysteine + an N5-methyl-tetrahydrofolate → L-methionine + a tetrahydrofolate

polymyxin resistance :
UDP-4-amino-4-deoxy-β-L-arabinopyranose + an N10-formyl-tetrahydrofolate → UDP-4-deoxy-4-formamido-β-L-arabinopyranose + a tetrahydrofolate + H+

purine nucleobases degradation I (anaerobic) , purine nucleobases degradation II (anaerobic) :
an N10-formyl-tetrahydrofolate + H2O → a tetrahydrofolate + formate + H+

pyoverdine I biosynthesis :
N5-hydroxy-L-ornithine + an N10-formyl-tetrahydrofolate → N5-formyl-N5-hydroxy-L-ornithine + a tetrahydrofolate

pyrimidine deoxyribonucleotides de novo biosynthesis III :
dUMP + a 5,10-methylene-tetrahydrofolate + NADPH + H+ → dTMP + a tetrahydrofolate + NADP+

tetrahydrofolate biosynthesis :
a tetrahydrofolate + NADP+ ← a 7,8-dihydrofolate + NADPH + H+

Not in pathways:
an N10-formyl-tetrahydrofolate + L-methionyl-tRNAfmeta tetrahydrofolate + N-formyl-L-methionyl-tRNAfmet

Reactions known to both consume and produce the compound:

5-aminoimidazole ribonucleotide biosynthesis I , tetrahydrofolate salvage from 5,10-methenyltetrahydrofolate :
an N10-formyl-tetrahydrofolate + N1-(5-phospho-β-D-ribosyl)glycinamide ↔ a tetrahydrofolate + N2-formyl-N1-(5-phospho-β-D-ribosyl)glycinamide + H+

folate polyglutamylation , formaldehyde assimilation I (serine pathway) , glycine betaine degradation I , glycine betaine degradation II (mammalian) , glycine biosynthesis I :
L-serine + a tetrahydrofolate ↔ glycine + a 5,10-methylene-tetrahydrofolate + H2O

folate transformations I :
glycine + a tetrahydrofolate + NAD+ ↔ a 5,10-methylene-tetrahydrofolate + ammonium + CO2 + NADH
L-serine + a tetrahydrofolate ↔ glycine + a 5,10-methylene-tetrahydrofolate + H2O

folate transformations II :
glycine + a tetrahydrofolate + NAD+ ↔ a 5,10-methylene-tetrahydrofolate + ammonium + CO2 + NADH
L-serine + a tetrahydrofolate ↔ glycine + a 5,10-methylene-tetrahydrofolate + H2O

glycine cleavage :
a [glycine-cleavage complex H protein] N6-aminomethyldihydrolipoyl-L-lysine + a tetrahydrofolate ↔ a [glycine-cleavage complex H protein] N6-dihydrolipoyl-L-lysine + a 5,10-methylene-tetrahydrofolate + ammonium

inosine-5'-phosphate biosynthesis I , inosine-5'-phosphate biosynthesis II :
an N10-formyl-tetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide ↔ a tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)-imidazole-4-carboxamide

N10-formyl-tetrahydrofolate biosynthesis :
glycine + a tetrahydrofolate + NAD+ ↔ a 5,10-methylene-tetrahydrofolate + ammonium + CO2 + NADH
L-serine + a tetrahydrofolate ↔ glycine + a 5,10-methylene-tetrahydrofolate + H2O

phosphopantothenate biosynthesis I :
a 5,10-methylene-tetrahydrofolate + 3-methyl-2-oxobutanoate + H2O ↔ 2-dehydropantoate + a tetrahydrofolate

photorespiration :
glycine + a tetrahydrofolate + NAD+ ↔ a 5,10-methylene-tetrahydrofolate + ammonium + CO2 + NADH
L-serine + a tetrahydrofolate ↔ glycine + a 5,10-methylene-tetrahydrofolate + H2O

purine nucleobases degradation I (anaerobic) :
a 5-formiminotetrahydrofolate + glycine ↔ N-formimino-glycine + a tetrahydrofolate

purine nucleobases degradation II (anaerobic) :
L-serine + a tetrahydrofolate ↔ glycine + a 5,10-methylene-tetrahydrofolate + H2O
a 5-formiminotetrahydrofolate + glycine ↔ N-formimino-glycine + a tetrahydrofolate

reductive acetyl coenzyme A pathway :
a tetrahydrofolate + a [methyl-Co(III) corrinoid Fe-S protein] ↔ an N5-methyl-tetrahydrofolate + a [Co(I) corrinoid Fe-S protein]

In Reactions of unknown directionality:

methylthiopropionate degradation II (demethylation) :
3-(methylthio)propanoate + a tetrahydrofolate = 3-mercaptopropionate + an N5-methyl-tetrahydrofolate

Not in pathways:
a 5,10-methylene-tetrahydrofolate + a uracil54 in tRNA + FADH2 = a tetrahydrofolate + a 5-methyluracil54 in tRNA + FAD + H+
dCMP + a 5,10-methylene-tetrahydrofolate + H2O = 2'-deoxy-5-hydroxymethylcytidine 5'-phosphate + a tetrahydrofolate
a 5,10-methylene-tetrahydrofolate + D-alanine + H2O = 2-methylserine + a tetrahydrofolate
an N10-formyl-tetrahydrofolate + NADP+ + H2O = a tetrahydrofolate + CO2 + NADPH + H+

Enzymes inhibited by tetrahydropteroyl mono-L-glutamate, sorted by the type of inhibition, are:

Inhibitor (Competitive) of: formimidoyltetrahydrofolate cyclodeaminase [Uyeda67a]

Inhibitor (Mechanism unknown) of: 3-methyl-2-oxobutanoate hydroxymethyltransferase [Powers76, Comment 1]

Inhibitor (Other types) of: methionine synthase [Banerjee90]

This compound has been characterized as a cofactor or prosthetic group of the following enzymes: serine hydroxymethyltransferase , sarcosine oxidase


References

Banerjee90: Banerjee RV, Frasca V, Ballou DP, Matthews RG (1990). "Participation of cob(I) alamin in the reaction catalyzed by methionine synthase from Escherichia coli: a steady-state and rapid reaction kinetic analysis." Biochemistry 1990;29(50);11101-9. PMID: 2271698

Hanson02: Hanson AD, Gregory JF (2002). "Synthesis and turnover of folates in plants." Curr Opin Plant Biol 5(3);244-9. PMID: 11960743

Jabrin03: Jabrin S, Ravanel S, Gambonnet B, Douce R, Rebeille F (2003). "One-carbon metabolism in plants. Regulation of tetrahydrofolate synthesis during germination and seedling development." Plant Physiol 131(3);1431-9. PMID: 12644692

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Lucock00: Lucock M (2000). "Folic acid: nutritional biochemistry, molecular biology, and role in disease processes." Mol Genet Metab 71(1-2);121-38. PMID: 11001804

Powers76: Powers SG, Snell EE (1976). "Ketopantoate hydroxymethyltransferase. II. Physical, catalytic, and regulatory properties." J Biol Chem 1976;251(12);3786-93. PMID: 6463

Uyeda67a: Uyeda K, Rabinowitz JC (1967). "Metabolism of formiminoglycine. Formiminotetrahydrofolate cyclodeaminase." J Biol Chem 242(1);24-31. PMID: 6016330


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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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