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Pathway Description
One Carbon Pool by Folate
Escherichia coli
Metabolic Pathway
Dihydrofolic acid, a product of the folate biosynthesis pathway, can be metabolized by multiple enzymes.
Dihydrofolic acid can be reduced by a NADP-driven dihydrofolate reductase resulting in a NADPH, hydrogen ion and folic acid.
Dihydrofolic acid can also be reduced by an NADPH-driven dihydrofolate reductase resulting in a NADP and a tetrahydrofolic acid. Folic acid can also produce a tetrahydrofolic acid through a NADPH-driven dihydrofolate reductase.
Dihydrofolic acid also interacts with 5-thymidylic acid through a thymidylate synthase resulting in the release of dUMP and 5,10-methylene-THF
Tetrahydrofolic acid can be converted into 5,10-methylene-THF through two different reversible reactions.
Tetrahydrofolic acid interacts with a S-Aminomethyldihydrolipoylprotein through a aminomethyltransferase resulting in the release of ammonia, a dihydrolipoylprotein and 5,10-Methylene-THF
Tetrahydrofolic acid interacts with L-serine through a glycine hydroxymethyltransferase resulting in a glycine, water and 5,10-Methylene-THF.
The compound 5,10-methylene-THF reacts with an NADPH dependent methylenetetrahydrofolate reductase [NAD(P)H] resulting in NADP and 5-Methyltetrahydrofolic acid. This compound interacts with homocysteine through a methionine synthase resulting in L-methionine and tetrahydrofolic acid.
Tetrahydrofolic acid can be metabolized into 10-formyltetrahydrofolate through 4 different enzymes:
1.- Tetrahydrofolic acid interacts with FAICAR through a phosphoribosylaminoimidazolecarboxamide formyltransferase resulting in a 1-(5'-Phosphoribosyl)-5-amino-4-imidazolecarboxamide and a 10-formyltetrahydrofolate
2.-Tetrahydrofolic acid interacts with 5'-Phosphoribosyl-N-formylglycinamide through a phosphoribosylglycinamide formyltransferase 2 resulting in a Glycineamideribotide and a 10-formyltetrahydrofolate
3.-Tetrahydrofolic acid interacts with Formic acid through a formyltetrahydrofolate hydrolase resulting in water and a 10-formyltetrahydrofolate
4.-Tetrahydrofolic acid interacts with N-formylmethionyl-tRNA(fMet) through a 10-formyltetrahydrofolate:L-methionyl-tRNA(fMet) N-formyltransferase resulting in a L-methionyl-tRNA(Met) and a 10-formyltetrahydrofolate
10-formyltetrahydrofolate can interact with a hydrogen ion through a bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase resulting in water and
5,10-methenyltetrahydrofolic acid.
Tetrahydrofolic acid can be metabolized into 5,10-methenyltetrahydrofolic acid by reacting with a
5'-phosphoribosyl-a-N-formylglycineamidine through a phosphoribosylglycinamide formyltransferase 2 resulting in water, glycineamideribotide and 5,10-methenyltetrahydrofolic acid. The latter compound can either interact with water through an aminomethyltransferase resulting in a N5-Formyl-THF, or it can interact with a NADPH driven bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase resulting in a NADP and 5,10-Methylene THF.
References
One Carbon Pool by Folate References
Bognar AL, Osborne C, Shane B, Singer SC, Ferone R: 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 May 10;260(9):5625-30.
Pubmed: 2985605
Giladi M, Altman-Price N, Levin I, Levy L, Mevarech M: FolM, a new chromosomally encoded dihydrofolate reductase in Escherichia coli. J Bacteriol. 2003 Dec;185(23):7015-8.
Pubmed: 14617668
GRIFFIN MJ, BROWN GM: THE BIOSYNTHESIS OF FOLIC ACID. III. ENZYMATIC FORMATION OF DIHYDROFOLIC ACID FROM DIHYDROPTEROIC ACID AND OF TETRAHYDROPTEROYLPOLYGLUTAMIC ACID COMPOUNDS FROM TETRAHYDROFOLIC ACID. J Biol Chem. 1964 Jan;239:310-6.
Pubmed: 14114858
Pyne C, Bognar AL: Replacement of the folC gene, encoding folylpolyglutamate synthetase-dihydrofolate synthetase in Escherichia coli, with genes mutagenized in vitro. J Bacteriol. 1992 Mar;174(6):1750-9.
Pubmed: 1548226
Richey DP, Brown GM: The biosynthesis of folic acid. IX. Purification and properties of the enzymes required for the formation of dihydropteroic acid. J Biol Chem. 1969 Mar 25;244(6):1582-92.
Pubmed: 4304228
Swedberg G, Fermer C, Skold O: Point mutations in the dihydropteroate synthase gene causing sulfonamide resistance. Adv Exp Med Biol. 1993;338:555-8.
Pubmed: 8304179
Vasudevan SG, Paal B, Armarego WL: Dihydropteridine reductase from Escherichia coli exhibits dihydrofolate reductase activity. Biol Chem Hoppe Seyler. 1992 Oct;373(10):1067-73.
Pubmed: 1418677
Vedantam G, Guay GG, Austria NE, Doktor SZ, Nichols BP: Characterization of mutations contributing to sulfathiazole resistance in Escherichia coli. Antimicrob Agents Chemother. 1998 Jan;42(1):88-93.
Pubmed: 9449266
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