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Pathway Description
One Carbon Pool by Folate
Escherichia coli 042
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2025-03-18
Last Updated: 2025-03-18
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
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Itoh T, Aiba H, Baba T, Hayashi K, Inada T, Isono K, Kasai H, Kimura S, Kitakawa M, Kitagawa M, Makino K, Miki T, Mizobuchi K, Mori H, Mori T, Motomura K, Nakade S, Nakamura Y, Nashimoto H, Nishio Y, Oshima T, Saito N, Sampei G, Seki Y, Horiuchi T, et al.: A 460-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 40.1-50.0 min region on the linkage map. DNA Res. 1996 Dec 31;3(6):379-92. doi: 10.1093/dnares/3.6.379.
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D'Ari L, Rabinowitz JC: Purification, characterization, cloning, and amino acid sequence of the bifunctional enzyme 5,10-methylenetetrahydrofolate dehydrogenase/5,10-methenyltetrahydrofolate cyclohydrolase from Escherichia coli. J Biol Chem. 1991 Dec 15;266(35):23953-8.
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Breazeale SD, Ribeiro AA, Raetz CR: Oxidative decarboxylation of UDP-glucuronic acid in extracts of polymyxin-resistant Escherichia coli. Origin of lipid a species modified with 4-amino-4-deoxy-L-arabinose. J Biol Chem. 2002 Jan 25;277(4):2886-96. doi: 10.1074/jbc.M109377200. Epub 2001 Nov 8.
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Pubmed: 9205837
Nagy PL, McCorkle GM, Zalkin H: purU, a source of formate for purT-dependent phosphoribosyl-N-formylglycinamide synthesis. J Bacteriol. 1993 Nov;175(21):7066-73. doi: 10.1128/jb.175.21.7066-7073.1993.
Pubmed: 8226647
Bosl M, Kersten H: Organization and functions of genes in the upstream region of tyrT of Escherichia coli: phenotypes of mutants with partial deletion of a new gene (tgs). J Bacteriol. 1994 Jan;176(1):221-31. doi: 10.1128/jb.176.1.221-231.1994.
Pubmed: 8282700
Oshima T, Aiba H, Baba T, Fujita K, Hayashi K, Honjo A, Ikemoto K, Inada T, Itoh T, Kajihara M, Kanai K, Kashimoto K, Kimura S, Kitagawa M, Makino K, Masuda S, Miki T, Mizobuchi K, Mori H, Motomura K, Nakamura Y, Nashimoto H, Nishio Y, Saito N, Horiuchi T, et al.: A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 12.7-28.0 min region on the linkage map. DNA Res. 1996 Jun 30;3(3):137-55. doi: 10.1093/dnares/3.3.137.
Pubmed: 8905232
Aiba A, Mizobuchi K: Nucleotide sequence analysis of genes purH and purD involved in the de novo purine nucleotide biosynthesis of Escherichia coli. J Biol Chem. 1989 Dec 15;264(35):21239-46.
Pubmed: 2687276
Flannigan KA, Hennigan SH, Vogelbacker HH, Gots JS, Smith JM: Purine biosynthesis in Escherichia coli K12: structure and DNA sequence studies of the purHD locus. Mol Microbiol. 1990 Mar;4(3):381-92. doi: 10.1111/j.1365-2958.1990.tb00605.x.
Pubmed: 2192230
Blattner FR, Burland V, Plunkett G 3rd, Sofia HJ, Daniels DL: Analysis of the Escherichia coli genome. IV. DNA sequence of the region from 89.2 to 92.8 minutes. Nucleic Acids Res. 1993 Nov 25;21(23):5408-17. doi: 10.1093/nar/21.23.5408.
Pubmed: 8265357
Meinnel T, Guillon JM, Mechulam Y, Blanquet S: The Escherichia coli fmt gene, encoding methionyl-tRNA(fMet) formyltransferase, escapes metabolic control. J Bacteriol. 1993 Feb;175(4):993-1000. doi: 10.1128/jb.175.4.993-1000.1993.
Pubmed: 8432722
Guillon JM, Mechulam Y, Schmitter JM, Blanquet S, Fayat G: Disruption of the gene for Met-tRNA(fMet) formyltransferase severely impairs growth of Escherichia coli. J Bacteriol. 1992 Jul;174(13):4294-301. doi: 10.1128/jb.174.13.4294-4301.1992.
Pubmed: 1624424
Old IG, Margarita D, Glass RE, Saint Girons I: Nucleotide sequence of the metH gene of Escherichia coli K-12 and comparison with that of Salmonella typhimurium LT2. Gene. 1990 Mar 1;87(1):15-21. doi: 10.1016/0378-1119(90)90490-i.
Pubmed: 2185137
Banerjee RV, Johnston NL, Sobeski JK, Datta P, Matthews RG: Cloning and sequence analysis of the Escherichia coli metH gene encoding cobalamin-dependent methionine synthase and isolation of a tryptic fragment containing the cobalamin-binding domain. J Biol Chem. 1989 Aug 15;264(23):13888-95.
Pubmed: 2668277
Drummond JT, Loo RR, Matthews RG: Electrospray mass spectrometric analysis of the domains of a large enzyme: observation of the occupied cobalamin-binding domain and redefinition of the carboxyl terminus of methionine synthase. Biochemistry. 1993 Sep 14;32(36):9282-9. doi: 10.1021/bi00087a004.
Pubmed: 8369296
Saint-Girons I, Duchange N, Zakin MM, Park I, Margarita D, Ferrara P, Cohen GN: Nucleotide sequence of metF, the E. coli structural gene for 5-10 methylene tetrahydrofolate reductase and of its control region. Nucleic Acids Res. 1983 Oct 11;11(19):6723-32. doi: 10.1093/nar/11.19.6723.
Pubmed: 6356036
Plunkett G 3rd, Burland V, Daniels DL, Blattner FR: Analysis of the Escherichia coli genome. III. DNA sequence of the region from 87.2 to 89.2 minutes. Nucleic Acids Res. 1993 Jul 25;21(15):3391-8. doi: 10.1093/nar/21.15.3391.
Pubmed: 8346018
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0001750
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