Subsystem: Pyruvate metabolism II: acetyl-CoA, acetogenesis from pyruvate

This subsystem's description is:

Due to its complexity, the [Pyruvate / Acetyl-CoP / Acetyl-P / Acetate] node of central metabolism is encoded in 3 Subsystems (SS): (i) Pyruvate:ferredoxin oxidoreductase, (ii) Fermentations: Mixed acid, and (iii) this SS: Pyruvate metabolism II: acetyl-CoA, acetogenesis from pyruvate. The combination of VARIANT CODES of all three SSs provides a draft model of this node in each organism. Variant codes for this SSs (only) are explained below.

Decarboxylation of pyruvate to acetyl-CoA can occur oxidatively under aerobic conditions and nonoxidatively under anaerobic conditions. Oxidative decarboxylation, a reaction catalyzed by the pyruvate dehydrogenase complex (PDH), functions primarily during respiratory metabolism, although some function may be retained during anaerobiosis (e.g. see Wagner et al., 2005). During anaerobiosis various microorganisms perform nonoxidative decarboxylation of pyruvate to acetyl-CoA by means of pyruvate formate-lyase (PFL) or Pyruvate:ferredoxin (flavodoxin) oxidoreductase. Pyruvate decarboxylase (EC catalyzes non-oxidative decarboxylation of pyruvate to acetaldehyde. In addition, Pyruvate oxidases catalyze the following reactions:
Pyruvate -> Acetate + CO2 (EC or
Pyruvate -> Acetyl-P + CO2 + H2O2 (EC The roles of these enzymes in metabolism are not completely clear, and are currently under intense investigation (Abdel-Hamid et al., 2005; Schreiner et al., 2005; Schreiner et al., 2006).

In the majority of eubacteria acetate dissimilation is catalyzed by PTA-ACK pathway (Phosphate acetyltransferase + Acetate kinase). This reversible pathway can also assimilate acetate, but only when it is present in relatively large concentrations and predominantly functions in the catabolic direction in vivo.
In all acetate-forming Archaea studied so far, the conversion of acetyl-CoA to acetate and the formation of ATP from ADP and phosphate are catalyzed by a single enzyme, an Acetyl-CoA synthetase (ADP-forming) (Brasen et al., 2001). This enzyme represents a novel mechanism of ATP synthesis by the mechanism of substrate-level phosphorylation. ADP-forming acetyl-CoA synthetase is also present in the eukaryotic protists Entamoeba histolytica and Giardia lamblia, and homologous proteins have been found in the genomes of several bacteria (see in Musfeldt et al. 1999; Sanchez et al. 2000). The metabolic function of these putative synthetases in bacteria remains to be demonstrated. Similarity of these proteins with Protein acetyltransferase, regulating AMP-forming Acetyl-CoA synthetase (Starai et al., 2004) is intriguing.

The catabolism of acetic acid in microorganisms involves condensation of this compound with CoA to form acetyl-CoA (Ac-CoA) in the presence of ATP and Mg (Wolfe, 2005). Acetyl-coenzyme A synthetase (AMP-forming, EC catalyzes this process in eubacteria and archaea alike. Although reversible in vitro, this reaction is irreversible in vivo due to the presence of intracellular pyrophosphatases (Wolfe, 2005) and serves as the main route of acetate assimilation. The reversible PTA-ACK pathway can assimilate acetate as well, but only in relatively large concentrations.
Note that acetate ActP transporter (Gimenez et al., 2003) is often clustered with Acetyl-CoA synthetase (AMP-forming).
Putative components of the Sir2-like protein acetylation/deacetylation regulatory system for Acetyl-CoA synthetase (Starai et al., 2002 & 2004) are also included in this SS: (i) NAD-dependent protein deacetylase of SIR2 family, (ii) Protein acetyltransferase. A different, NAD-independent acetylation/deacetylation regulatory system that uses AcsA as a substrate has been recently described in B. subtilis (Gardner et al., 2006). Itís orthologs present in many Firmicutes are annotated here as: (iii) Acetyltransferase AcuA, acetyl-CoA synthetase inhibitor and (iv) NAD-independent protein deacetylase AcuC. The role of AcuB located in the same cluster remains unclear (Gardner et al., 2006)

Acetyl-P is a central metabolite of vital importance for ATP generation via substrate phosphorylation, as well as several proposed energy-related and signaling roles (Wolfe, 2005). In addition to PAT and ACK, other enzymes evolving acetyl~P are included in this SS as auxiliary functional roles (SSs encoding them in detail are given below):

(i) Pyruvate oxidase (EC Pyr + O2 = Acetyl~P + CO2 + H2O2 (this SS)
(ii) Xylulose-5-phosphate phosphoketolase (EC Xylulose-5P + Pi <=> Acetyl~P + Glyceraldehyde-3P+ H2O. See SS: Fermentation: Lactate for details.
(iii) Fructose-6-phosphate phosphoketolase (EC Fructose-6P + Pi <=> Acetyl~P Erythrose-4P + H2O. See SS: Fermentation: Lactate for details.
(iv) Sulfoacetaldehyde acetyltransferase (XSC, EC Sulfoacetaldehyde + HPO4 = HSO3 + Acetyl~P (dissimilation of sulfonated compounds). Enzyme is widespread in Proteobact and at least a couple Gram(+)s. In most organisms tested PAT is located in immediate vicinity of XSC
(v) Glycine reductase (EC -- present in some strict anaerobes (Arkowitz, Abeles, 1991). It catalyzes acetyl~P production during reductive deamination of glycine, sarcosine, or betaine :
Glycine + Pi + Thioredoxin = Acetyl~P+ NH3 + Thioredoxin disulfide. See SS: Glycine reductase, sarcosine reductase and betaine reductase.

In many organisms these enzymes are located in immediate vicinity of PAT or ACT, suggesting that Acetyl~P formed could be converted by PAT to Acetyl-CoA for anabolism or utilized as P-donor by ACK for ATP generation (Ruff et al., 2003; Wolfe, 2005).

in S. pneumoniae, lactate oxidase converts lactate, usually regarded as a dead-end product of glucose metabolism in this organism, back to pyruvate, which is then subject to oxidation by pyruvate oxidase to form acetyl phosphate. Based on this finding, it was proposed that the two H2O2-producing oxidases (pyruvate and lactate) act in a concerted manner in the presence of oxygen to obtain a greater amount of energy from glucose than under anaerobiosis, with acetate rather than lactate being the final product of the system (Taniai, Iida, et al.2008)

This subsystem has been initially encoded by master:LienC_UCSD as Acetogenesis_from_Pyruvate.

For more information, please check out the description and the additional notes tabs, below

Literature ReferencesControl of acetyl-coenzyme A synthetase (AcsA) activity by acetylation/deacetylation without NAD(+) involvement in Bacillus subtilis. Gardner JG Journal of bacteriology 2006 Aug16855235
In Bacillus subtilis, the sirtuin protein deacetylase, encoded by the srtN gene (formerly yhdZ), and functions encoded by the acuABC genes control the activity of acetyl coenzyme A synthetase. Gardner JG Journal of bacteriology 2009 Mar19136592
DiagramFunctional RolesSubsystem SpreadsheetDescriptionAdditional NotesScenarios 

Oops! We thought there was a diagram here, but we can't find it. Sorry

Group Alias
Abbrev.Functional RoleReactionsScenario ReactionsGOLiterature

display  items per page
«first  «prevdisplaying 1 - 3130 of 3130next»  last»
Taxonomy Pattern