Escherichia coli K-12 substr. MG1655 Pathway: gluconeogenesis I
Traceable author statement to experimental supportInferred from experiment

Pathway diagram: gluconeogenesis I

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Locations of Mapped Genes:

Schematic showing all replicons, marked with selected genes

Genetic Regulation Schematic

Genetic regulation schematic for gluconeogenesis I

Superclasses: BiosynthesisCarbohydrates BiosynthesisSugars BiosynthesisGluconeogenesis

Escherichia coli uses gluconeogenesis to synthesize glucose 6-phosphate from non-carbohydrate carbon substrates when sufficient amounts of exogenous glucose or other sugars are unavailable for transport into the cell. Carbon sources for gluconeogenesis include 3-carbon compounds such as pyruvate, (S)-lactate and glycerol, or intermediates of the TCA cycle such as (S)-malate, and oxaloacetate. The glucose 6-phosphate end product of gluconeogenesis is a precursor of glycogen and various sugars used in the biosynthesis of cell surface structures. Several important intermediates synthesized during gluconeogenesis, fructose 6-phosphate phosphoenolpyruvate (PEP) and 3-phosphoglycerate, also serve as biosynthetic precursors. For example see pathways glycogen biosynthesis I (from ADP-D-Glucose), UDP-N-acetyl-D-glucosamine biosynthesis I, 3-dehydroquinate biosynthesis I, and L-serine biosynthesis.

In E. coli the gluconeogenesis pathway is essentially a reversal of glycolysis and requires energy input in the form of ATP and NADH(H+) to produce the 6-carbon molecule glucose 6-phosphate from 3- or 4-carbon precursors. During gluconeogenesis two enzyme activities catalyze irreversible reactions that enable the glycolysis pathway to flow in the opposite direction to produce glucose 6-phosphate. These uniquely gluconeogenic enzymes are fructose 1,6-bisphosphatase EC, and pyruvate, water dikinase (also known as PEP synthetase) EC Their unidirectionally opposite counterparts in the glycolysis pathway are 6-phosphofructokinase EC and pyruvate kinase EC, respectively (see pathway glycolysis I (from glucose 6-phosphate)).

The gluconeogenesis pathway enzymes fructose 1,6-bisphosphatase and PEP synthetase, along with PEP carboxykinase and the malic enzymes encoded by maeA and maeB, catalyze anaplerotic reactions, defined as those that replenish pools of metabolic intermediates. The first committed step of gluconeogenesis is the formation of PEP. This is catalyzed by PEP carboxykinase encoded by pck, or PEP synthetase encoded by ppsA, both in physiologically unidirectional reactions. These enzymes exert control over gluconeogenic growth on different carbon sources [Chao93].

To meet the cell's energy needs under various conditions, coordinate regulation of gluconeogeneis and glycolysis is necessary [Peng03]. For example, at the protein level the presence of pyruvate protects PEP synthetase from inactivation by regulatory protein PSRP [Burnell10]. The fructose 1,6-bisphosphatase isozyme encoded by fbp is allosterically regulated, being activated by PEP and inhibited by AMP [Hines06]. At the transcriptional level genes glpX, yggF, ppsA, pck and glk have been identified as targets for the transcription factor CRP which is activated by cAMP in the absence of glucose and has a major role in the switch between glycolysis and gluconeogenesis [Shimada11a]. The carbon storage regulator CsrA was found to exert reciprocal effects on glycolysis which is positively regulated, versus gluconeogenesis and glycogen biosynthesis which are negatively regulated by this protein [Sabnis95].

Review: [Sauer05]

Created 13-May-1994 by Riley M, Marine Biological Laboratory


Burnell10: Burnell JN (2010). "Cloning and characterization of Escherichia coli DUF299: a bifunctional ADP-dependent kinase - phosphate-dependent pyrophosphorylase from bacteria." BMC Biochem 11(1);1. PMID: 20044937

Chao93: Chao YP, Patnaik R, Roof WD, Young RF, Liao JC (1993). "Control of gluconeogenic growth by pps and pck in Escherichia coli." J Bacteriol 175(21);6939-44. PMID: 8226637

Hines06: Hines JK, Fromm HJ, Honzatko RB (2006). "Novel allosteric activation site in Escherichia coli fructose-1,6-bisphosphatase." J Biol Chem 281(27);18386-93. PMID: 16670087

Peng03: Peng L, Shimizu K (2003). "Global metabolic regulation analysis for Escherichia coli K12 based on protein expression by 2-dimensional electrophoresis and enzyme activity measurement." Appl Microbiol Biotechnol 61(2);163-78. PMID: 12655459

Sabnis95: Sabnis NA, Yang H, Romeo T (1995). "Pleiotropic regulation of central carbohydrate metabolism in Escherichia coli via the gene csrA." J Biol Chem 1995;270(49);29096-104. PMID: 7493933

Sauer05: Sauer U, Eikmanns BJ (2005). "The PEP-pyruvate-oxaloacetate node as the switch point for carbon flux distribution in bacteria." FEMS Microbiol Rev 29(4);765-94. PMID: 16102602

Shimada11a: Shimada T, Fujita N, Yamamoto K, Ishihama A (2011). "Novel roles of cAMP receptor protein (CRP) in regulation of transport and metabolism of carbon sources." PLoS One 6(6);e20081. PMID: 21673794

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Aguilera09: Aguilera L, Gimenez R, Badia J, Aguilar J, Baldoma L (2009). "NAD+-dependent post-translational modification of Escherichia coli glyceraldehyde-3-phosphate dehydrogenase." Int Microbiol 12(3);187-92. PMID: 19784925

Ahn11: Ahn J, Chung BK, Lee DY, Park M, Karimi IA, Jung JK, Lee H (2011). "NADPH-dependent pgi-gene knockout Escherichia coli metabolism producing shikimate on different carbon sources." FEMS Microbiol Lett 324(1);10-6. PMID: 22092758

AitBara10: Ait-Bara S, Carpousis AJ (2010). "Characterization of the RNA degradosome of Pseudoalteromonas haloplanktis: conservation of the RNase E-RhlB interaction in the gammaproteobacteria." J Bacteriol 192(20);5413-23. PMID: 20729366

Al12: Al Mamun AA, Lombardo MJ, Shee C, Lisewski AM, Gonzalez C, Lin D, Nehring RB, Saint-Ruf C, Gibson JL, Frisch RL, Lichtarge O, Hastings PJ, Rosenberg SM (2012). "Identity and function of a large gene network underlying mutagenic repair of DNA breaks." Science 338(6112);1344-8. PMID: 23224554

Alakent11: Alakent B, Baskan S, Doruker P (2011). "Effect of ligand binding on the intraminimum dynamics of proteins." J Comput Chem 32(3);483-96. PMID: 20730777

Albin84: Albin R, Silverman PM (1984). "Physical and genetic structure of the glpK-cpxA interval of the Escherichia coli K-12 chromosome." Mol Gen Genet 197(2);261-71. PMID: 6097795

Alefounder89: Alefounder PR, Perham RN (1989). "Identification, molecular cloning and sequence analysis of a gene cluster encoding the class II fructose 1,6-bisphosphate aldolase, 3-phosphoglycerate kinase and a putative second glyceraldehyde 3-phosphate dehydrogenase of Escherichia coli." Mol Microbiol 3(6);723-32. PMID: 2546007

Alefounder89a: Alefounder PR, Baldwin SA, Perham RN, Short NJ (1989). "Cloning, sequence analysis and over-expression of the gene for the class II fructose 1,6-bisphosphate aldolase of Escherichia coli." Biochem J 1989;257(2);529-34. PMID: 2649077

Alvarez98: Alvarez M, Zeelen JP, Mainfroid V, Rentier-Delrue F, Martial JA, Wyns L, Wierenga RK, Maes D (1998). "Triose-phosphate isomerase (TIM) of the psychrophilic bacterium Vibrio marinus. Kinetic and structural properties." J Biol Chem 273(4);2199-206. PMID: 9442062

Amarneh05: Amarneh B, Vik SB (2005). "Direct transfer of NADH from malate dehydrogenase to complex I in Escherichia coli." Cell Biochem Biophys 42(3);251-61. PMID: 15976458

Anderson69: Anderson A, Cooper RA (1969). "Gluconeogenesis in Escherichia coli The role of triose phosphate isomerase." FEBS Lett 4(1);19-20. PMID: 11947134

Arifuzzaman06: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699

Babul83: Babul J, Guixe V (1983). "Fructose bisphosphatase from Escherichia coli. Purification and characterization." Arch Biochem Biophys 1983;225(2);944-9. PMID: 6312898

Babul88: Babul J, Fraenkel DG (1988). "Phosphate modification of fructose-1,6-bisphosphate aldolase in Escherichia coli." Biochem Biophys Res Commun 151(3);1033-8. PMID: 3281666

Babul93: Babul J, Clifton D, Kretschmer M, Fraenkel DG (1993). "Glucose metabolism in Escherichia coli and the effect of increased amount of aldolase." Biochemistry 32(17);4685-92. PMID: 8485146

Bairoch93: Bairoch A, Boeckmann B (1993). "The SWISS-PROT protein sequence data bank, recent developments." Nucleic Acids Res. 21:3093-3096. PMID: 8332529

Baldwin78: Baldwin SA, Perham RN (1978). "Novel kinetic and structural properties of the class-I D-fructose 1,6-bisphosphate aldolase from Escherichia coli (Crookes' strain)." Biochem J 1978;169(3);643-52. PMID: 348198

Baldwin78a: Baldwin SA, Perham RN, Stribling D (1978). "Purification and characterization of the class-II D-fructose 1,6-bisphosphate aldolase from Escherichia coli (Crookes' strain)." Biochem J 1978;169(3);633-41. PMID: 417719

Bardey05: Bardey V, Vallet C, Robas N, Charpentier B, Thouvenot B, Mougin A, Hajnsdorf E, Regnier P, Springer M, Branlant C (2005). "Characterization of the molecular mechanisms involved in the differential production of erythrose-4-phosphate dehydrogenase, 3-phosphoglycerate kinase and class II fructose-1,6-bisphosphate aldolase in Escherichia coli." Mol Microbiol 57(5);1265-87. PMID: 16102000

Bazaes93: Bazaes S, Silva R, Goldie H, Cardemil E, Jabalquinto AM (1993). "Reactivity of cysteinyl, arginyl, and lysyl residues of Escherichia coli phosphoenolpyruvate carboxykinase against group-specific chemical reagents." J Protein Chem 12(5);571-7. PMID: 8141999

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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