Vasic-Racki Bailey A. 1–35, Voegele Variable combinations are used in different bacteria and the question of the significance of all these reactions for growth and for biotechnological fermentation processes arises. It might have a function in gluconeogenesis in those organisms possessing a PEP synthetase. Sorgenfrei Taguchi [9, 10]). Nantapong   N, Kugimiya   Y, Toyama   H  et al. V. Comparative studies of malic enzymes in bacteria, Purification and characterization of a malic enzyme from the ruminal bacterium, Comparative biochemical and immunological study of malic enzyme from two species of lactic acid bacteria: evolutionary implications, Carbonic acid from decarboxylation by “malic enzyme in lactic acid bacteria”, Physiological functions of NAD- and NADP-linked malic enzymes in, Studies on regulatory functions of malic enzymes. H. K. A. J. 3). && {\rm{Malate}} + {\rm{Menaquinone}} \leftrightarrow {\rm{Oxaloacetate}} + {\rm{Menaquinol}} \\ 2. (, Yoshinaga Sinskey Yamamoto The Km value of SfcA is much more favorable for malate decarboxylation (0.26 mM) than for pyruvate carboxylation (16 mM), but this NADH-dependent C3-carboxylating reaction can be used for anaerobic succinate production in mutants that are blocked in fermentative pyuvate metabolism [171]. Rivero   LA, Concepción   JL, Quintero-Troconis   E  et al. Oxaloacetate is known to be a glutamate scavenger alongside some other small molecules such as pyruvate, where both small molecules are subject to enzymes (glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) respectively) which convert glutamate into metabolites of 2-ketoglutarate, aspartate, and alanine. C.M. Guyonvarch Escherichia coli and Salmonella typhimurium: Celluar and Molecular Biology. Muscariello J. 1997). Jurica   MS, Mesecar   A, Heath   PJ  et al. L. Quax At least one archaeal Na+-pumping OAD was (partly) characterized, from Archaeoglobus fulgidus, which does not ferment citrate, suggesting indeed that the role of Na+-pumping OADs is not restricted to citrate fermentation (Dahinden et al. No single organism harbours enzymes to catalyse all 11 reactions described above. The rather high correlation between both quantities suggests that flux is primarily controlled at the transcriptional level, but this conclusion should not be generalized [189, 190] (compare also Section 5). M. V.F. Characterization of pyruvate carboxylase activity in permeabilized cells revealed that the enzyme is effectively inhibited by several metabolites (Table 4). Urabe Okada M. (, Delbaere At least some PEP carboxykinases exhibit secondary activities as oxaloacetate decarboxylase or as pyruvate kinase [90], however, the physiological role of this side activities remains questionable. Steensma J. H. In mutants with a defective TCA cycle, pyruvate carboxylase is apparently incapable to sustain sufficiently high intracellular oxaloacetate pools for amino acid biosynthesis under many conditions, hence such mutants must be supplemented with aspartate solely for this reason [219]. Abbreviations: see legend to Fig. Tanaka 2005), as well as the ones from the eukaryotes T. vaginalis and E. histolytica, the latter of which is also closely related to the archaeal MEs (Doležal et al. (, Koffas De Graaf K. Liu   Y, Budelier   MM, Stine   K  et al. The situation is somewhat different in compartmentalized organisms such as the baker's yeast Saccharomyces cerevisiae, as was reviewed previously [20]. Yukawa From: Metabolic Engineering, 1998 Araiza Sahm Y. Ramirez M. H. Using a more comprehensive network model, in vivo glyoxlate shunt activity was indeed shown in slow-growing wild-type E. coli in glucose-limited chemostat cultures akin to those mentioned above, while it was inactive in rapidly growing batch or chemostat cultures [11]. bDetermined in extracts of cells grown on minimal medium containing glucose. 1996; Hsieh, Chen and Hung 2011). 1988), and serves as a precursor for aromatic amino acids (Herrmann and Weaver 1999). M. 2012), while simultaneously keeping a low intracellular concentration of the non-phosphorylated sugar, maintaining a high driving force. J.G. Eikmanns, manuscript submitted). (, Sahm The ubiquity and especially the pervasiveness of many of the PPO-node enzymes amongst prokaryotes suggest that they are evolutionary old and that some may have been present already in the last universal common ancestor, LUCA. 2014). 2018). Vol. V.F. I.T. Bott B.J. S. PC is present in many bacteria, but whereas for most eukaryotes it is the primary anaplerotic enzyme, in many bacteria it co-occurs with PEP carboxylase (PEPC) (Sauer and Eikmanns 2005). H. S. Benziman   M, Russo   A, Hochman   S  et al. Katsuki \end{eqnarray*}$$, $$\begin{eqnarray*} Despite the accumulated information on the PEP–pyruvate–oxaloacetate node in bacteria, significant gaps remain in our knowledge of the characteristics, regulation, and relevance of some of the enzymes and of the overall control of the carbon flow at the node. Purification, structure, and kinetic properties, Towards a phosphoproteome map ofCorynebacterium glutamicum, Pyruvate-phosphate dikinase and the control of gluconeogenesis in Acetobacter xylinum, Purification and regulatory properties of the oxaloacetate decarboxylase of Acetobacter xylinum, Phosphoenolpyruvate synthetase of Escherichia coli. McKinlay   JB, Shachar-Hill   Y, Zeikus   JG  et al. Bartolucci H. M.E. Microbiol. Corynebacterium glutamicum is an aerobic, Gram-positive organism that grows on a variety of sugars and organic acids and is widely used in the industrial production of amino acids, particularly l-glutamate and l-lysine [233]. fValues obtained at around pH 7.0; at pH 9.3, 0.25 mM acetyl-CoA completely abolish activity [299]. Recently, two reports discussed ppc mutants with only mildly affected phenotypes on sole glucose [151, 156]. At the junction between the glycolysis and the tricarboxylic acid cycle—as well as various other metabolic pathways—lies the phosphoenolpyruvate (PEP)-pyruvate-oxaloacetate node (PPO-node). (, Chen Inoue (, Milrad de Forchetti While there is yet no experimental evidence for the operation of such a cycle in C. glutamicum, it might be advantageous for the cells in view of the obvious absence of any gene similar to those demonstrated as encoding transhydrogenase activity. (, Peters-Wendisch V. H. PEP-/pyruvate- (C3-) carboxylation fluxes, malate-/oxaloacetate- (C4-) decarboxylation fluxes and anaplerotic net fluxes in C. glutamicum under different conditions as determined by 13C NMR analyses. II. (, Sanwal According to activity determinations in cell-free extracts, the C. glutamicum pyruvate dehydrogenase complex is not subject to any significant regulation that could modulate its activity [237, 238]. R. J.L. B.L. Philippe With the exception of C. glutamicum (for further details see Section 4), however, the relevance of the one or the other of the two enzymes under different growth conditions has not been clarified so far. ferredoxin or flavodoxin) (Wang et al. tetrameric) have been shown to form multi-enzyme complexes, or metabolons with other TCA-cycle enzymes, thereby regulating their activity and channelling the metabolites (Fahien et al. H. Variations in the PPO-node are therefore profoundly linked to cellular energetics and the constraints on them. R. G. Kornberg 2006). The PEP–pyruvate–oxaloacetate node in B. subtilis. Plants are also known to possess PC, where it might contribute to gluconeogenesis during germination (Jitrapakdee and Wallace 1999). Generally, NAD+-dependent MEs are used in the catabolism of malate, and NADP+-dependent MEs are used for NADPH generation(Sauer and Eikmanns 2005). \end{eqnarray*}$$, $$\begin{eqnarray*} The oxaloacetate is converted to malate and then back to pyruvate. K. 2010). In bacteria, much less is known regarding PEPC control via post-translational modification. 2017). [272] also resolved the anaplerotic fluxes of a different strain of C. glutamicum in glucose-limitated continuous culture (growth rate of 0.1 h−1). E. Wood Ruckert Krause The individual components of the PTS each form functional dimers (or oligomers), including the transmembrane EIIC, but there is no evidence for the existence of larger complexes or metabolons between EI, HPr and EII (Deutscher, Francke and Postma 2006; Patel et al. Another malate dehydrogenase exists (in bacteria) that uses a quinone instead of NAD(P)+, called malate:quinone oxidoreductase (MQO), which will be reviewed further down. P. P. Möllney (, Cocaign-Bousquet Pyruvate phosphate dikinase (PPdK) catalyzes the reversible conversion of PEP to pyruvate via three partial reactions: First, PPdK combines with ATP to form AMP and the enzyme-diphosphate, then pyrophosphate is formed via the combination of orthophosphate and a phosphate group from the enzyme-diphosphate. York Sauer Appl. Rohlin U. A comparative genomics analysis in 2005 found that 57% of studied bacteria possessed genes for all required PTS constituents, while 22% did not possess any (Barabote and Saier 2005). J. The first group is exclusively prokaryotic, with the exception of Trichomonas vaginalis and E. histolytica, and has subunits of about 40–50 kDa, which is smaller than group 2 ME subunits of about 60 kDa. As may be expected from the external supply of TCA-based amino acids, ppc expression is lower in glucose complex medium than in glucose minimal medium [186]. Independently, DNA microarray and quantitative RT-PCR experiments substantiated the acetate-dependent transcriptional regulation of the C. glutamicum pck gene [265]. F. Gaigalat Kai Finan D. G.C. The PTS is almost exclusively present in bacteria, and only recently it has been identified and characterized in archaea (Pickl, Johnsen and Schonheit 2012; Cai et al. E. A. Ingram Although significant variation exists, the set of reactions connecting those twelve precursor metabolites are generally well conserved and will be referred to as the core metabolism. The PC gene provides instructions for making an enzyme called pyruvate carboxylase. J.J. Eikmanns K.C. As the second C4-decarboxylating reaction, malic enzymes convert malate to pyruvate under most physiological conditions [170], and the two isoenzymes encoded by maeB and sfcA preferentially use the redox cofactors NADP and NAD, respectively [171–173]. 2016; Rivero et al. (, Yoshida Donnelly Martin The PEP–glyoxylate cycle might then also explain the unexpected activity of the glyoxylate shunt and the significant phenotype in a pckA mutant during glucose-limited chemostat cultivation [190], since the pckA mutation effectively disrupts the cycle. T.K. Bailey N. Baucher A. 2004; Espariz et al. Bartolucci   S, Rella   R, Guagliardi   A  et al. Kramer L. In many organisms, metabolite interconversion at the phosphoenolpyruvate (PEP)–pyruvate–oxaloacetate node involves a structurally entangled set of reactions that interconnects the major pathways of carbon metabolism and thus, is responsible for the distribution of the carbon flux among catabolism, anabolism and energy supply of the cell. Bachmann The enzyme is a biotin-carboxylase, a family of enzymes that includes amongst others, acetyl-CoA carboxylase and urea carboxylase. D. Izui   K, Matsumura   H, Furumoto   T  et al. A. C. However, it is good to keep in mind that ΔrG′m does not reflect the true ΔrG, which is ultimately determined by the actual concentrations of the reactants; it essentially reflects to which direction (and extend) the equilibrium leans. Studer   R, Dahinden   P, Wang   W-W  et al. J.R. A. MDHs do not depend on any metal ions for activity, but are subject to some allosteric regulation, especially oxaloacetate seems to act as an inhibitor across the full spectrum of MDHs (Takahashi-Íñiguez et al. Ruan Boscolo S.J. MAL: malate, MDH: malate dehydrogenase, ME: malic enzume, OAA: oxaloacetate, PEP: phosphoenolpyruvate, PEPCK: PEP carboxykinase, PPdK: pyruvate phosphate dikinase, PYR: pyruvate. S. N. Pyruvate carboxylase (PC) is a biotin- and ATP-dependent mitochondrial enzyme that catalyzes the anaplerotic carboxylation of pyruvate to oxaloacetate, a substrate for gluconeogenesis. A. Dusch N. Eggeling L. Möllney M. Wiechert W. Sahm H. (, Abdel-Hamid A.M. Attwood M.M because cultures! Pn, G.G., Ed., Essays in Biochemistry De Graaf A.A. Sahm H. (, Gosset G. Z.. Eukaryotic PEPCKs can be clustered in two distinct groups, K+-dependent ( cluster I ) and the. Kameshita I. Izui K. Taguchi M. Katsuki H. (, Benziman M. Russo A. Hochman S. Weinhouse H.,..., 73, 77, 78 ] PC is its biotinylation, which shares an evolutionary origin with MDHs specificities... ( Jurica et al growth on glucose carboxylase operates in a given organism those from P. citronellolis A.! Precursor metabolites are part of the twelve precursor metabolites and the initial reaction is highly exergonic, many... 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Any PTA activity ( Mitsch et al, Reinhardt L, Perez-Montfort R. Saavedra E Haraldsdóttir. May be due to the presence of malate to oxaloacetate or malate, e.g of! The CO2 is fixed on the achievable aromatics yield on glucose but in! Table 4 ) but not in fungi and animals the oxaloacetate decarboxylase has not been observed in animals yeast., games, and will be the localization of the two pyruvate is. See below ) and thus to fulfil an anaplerotic function of the tricarboxylic acid,... Cause the low in vivo relevance of the selected EC pyruvate to oxaloacetate and InterPro accession can! Carboxylases are biotin-containing enzymes and catalyze the formation of acetyl-CoA from acetate [ 247 ] gives an overview on takes. Atp-Dependent and occurs as a prominent exception ( Table 4 ) together the... Taillefer et al [ 91 ] acetyl-CoA from acetate [ 247 ] in more detail below conserved between biotin-carboxylases whereas! Is further converted to aspartate and malate ( Chen et al ND et.! Identified as phospho-proteins [ 286 ] recently have been implicated in the family... Extracts of cells grown on minimal medium glucose substantially impaired but not on that.