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MetaCyc Pathway: acetate formation from acetyl-CoA III (succinate)
Inferred from experiment

Enzyme View:

Pathway diagram: acetate formation from acetyl-CoA III (succinate)

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Degradation/Utilization/AssimilationCarboxylates DegradationAcetate Formation
Generation of Precursor Metabolites and EnergyFermentationAcetate Formation

Some taxa known to possess this pathway include : Entamoeba histolytica, Fasciola hepatica, Leishmania infantum, Leishmania mexicana, Neocallimastix sp. LM-2, Phytomonas, Trichomonas vaginalis, Tritrichomonas suis, Trypanosoma brucei

Expected Taxonomic Range: Amoebozoa, Euglenozoa, Fungi, Parabasalia, Platyhelminthes

General Background

Acetate production from acetyl-CoA can occur via several distinct pathways, which are found in different organisms.

Many eubacteria produce acetate from acetyl CoA via a two-step pathway in which acetyl phosphate occurs as an intermediate (see acetate formation from acetyl-CoA I) [Brown77]. The second reaction, catalyzed by acetate kinase, results in the generation of ATP from ADP.

In archea [Mai96], some eubacteria (such as Selenomonas ruminantium [Michel90]), and amitochondriate protists (such as Entamoeba histolytica [Reeves77] and Giardia intestinalis [Sanchez96]) acetate is produced from acetyl CoA in a single step via the enzyme acetate-CoA ligase (ADP-forming). In this process, the formation of acetate from acetyl CoA concomitantly produces ATP from ADP (see acetate formation from acetyl-CoA II).

A third pathway ( acetate formation from acetyl-CoA III (succinate)) is found in a diverse group of organisms, which includes the hydrogenosome-containing trichomonads (such as Tritrichomonas suis and Trichomonas vaginalis [Steinbuchel86]), some anaerobic fungi (such as Neocallimastix sp. LM-2 [MarvinSikkema93]), the parasitic helminth Fasciola hepatica [Barrett78, vanVugt79, Saz96] and the trypanosomatides [Van98, Riviere04]. Theser organisms produce acetate from acetyl CoA by acetyl:succinate CoA-transferase (ASCT), an enzyme that transfers the CoA group from acetyl-CoA to succinate, producing succinyl-CoA. succinyl-CoA is restored to succinate by succinyl-CoA synthetase, a TCA cycle enzyme that generates ATP from ADP.

About This Pathway

Trypanosoma brucei, one of the causative agents of African trypanosomiasis (sleeping sickness), alternates during its life cycle between the bloodstream of its mammalian host and the blood-feeding tsetse fly, Glossina. The parasite exhibits different cellular morphology during its life cycle. In the mammalian bloodstream it exhibits a long, slender morphology, while in the insect host it exhibits a stubby morphology known as procyclic cells. Profound differences exist in the metabolism of the two life cycle phases.

In the procyclic stage the mitochondrion is directly involved in the degradation of substrates, in contrast to the situation in the long slender bloodstream stage. pyruvate enters the mitochondrion and is converted by the pyruvate decarboxylation to acetyl CoA into acetyl-CoA. This acetyl-CoA is not degraded to carbon dioxide via the TCA cycle I (prokaryotic), but is converted into acetate [Riviere04].

This reaction is carried out by acetyl:succinate CoA-transferase (ASCT), an enzyme that transfers the CoA group from acetyl-CoA to succinate, producing succinyl-CoA.

Several other organisms have been shown to catalyze this reaction, including the hydrogenosome-containing trichomonads (such as Tritrichomonas suis and Trichomonas vaginalis [Steinbuchel86]), some anaerobic fungi (such as Neocallimastix sp. LM-2[MarvinSikkema93]), and the parasitic helminth Fasciola hepatica [Barrett78, vanVugt79, Saz96].

A knockout mutant of Trypanosoma brucei depleted for ASCT showed a reduced acetate production, supporting the role of this enzyme in acetate production. However, ASCT mutants still excrete acetate from glucose metabolism, implying that ASCT is not the only acetate-producing pathway in this parasite [Riviere04].

Superpathways: pyruvate fermentation to acetate VI, pyruvate fermentation to acetate V, anaerobic energy metabolism (invertebrates, mitochondrial), superpathway of anaerobic energy metabolism (invertebrates)

Variants: acetate formation from acetyl-CoA I, acetate formation from acetyl-CoA II

Created 31-Jul-2007 by Caspi R, SRI International


Barrett78: Barrett J, Coles GC, Simpkin KG (1978). "Pathways of acetate and propionate production in adult Fasciola hepatica." Int J Parasitol 8(2);117-23. PMID: 681067

Brown77: Brown TD, Jones-Mortimer MC, Kornberg HL (1977). "The enzymic interconversion of acetate and acetyl-coenzyme A in Escherichia coli." J Gen Microbiol 1977;102(2);327-36. PMID: 21941

Mai96: Mai X, Adams MW (1996). "Purification and characterization of two reversible and ADP-dependent acetyl coenzyme A synthetases from the hyperthermophilic archaeon Pyrococcus furiosus." J Bacteriol 1996;178(20);5897-903. PMID: 8830684

MarvinSikkema93: Marvin-Sikkema FD, Pedro Gomes TM, Grivet JP, Gottschal JC, Prins RA (1993). "Characterization of hydrogenosomes and their role in glucose metabolism of Neocallimastix sp. L2." Arch Microbiol 160(5);388-96. PMID: 8257282

Michel90: Michel, T. A., Macy, J. M. (1990). "Purification of an enzyme responsible for acetate formation from acetyl coenzyme A in Selenomonas ruminatium." FEMS Microbiology Letters 68 (1-2): 189-194.

Reeves77: Reeves RE, Warren LG, Susskind B, Lo HS (1977). "An energy-conserving pyruvate-to-acetate pathway in Entamoeba histolytica. Pyruvate synthase and a new acetate thiokinase." J Biol Chem 252(2);726-31. PMID: 13076

Riviere04: Riviere L, van Weelden SW, Glass P, Vegh P, Coustou V, Biran M, van Hellemond JJ, Bringaud F, Tielens AG, Boshart M (2004). "Acetyl:succinate CoA-transferase in procyclic Trypanosoma brucei. Gene identification and role in carbohydrate metabolism." J Biol Chem 279(44);45337-46. PMID: 15326192

Sanchez96: Sanchez LB, Muller M (1996). "Purification and characterization of the acetate forming enzyme, acetyl-CoA synthetase (ADP-forming) from the amitochondriate protist, Giardia lamblia." FEBS Lett 378(3);240-4. PMID: 8557109

Saz96: Saz HJ, deBruyn B, de Mata Z (1996). "Acyl-CoA transferase activities in homogenates of Fasciola hepatica adults." J Parasitol 82(5);694-6. PMID: 8885873

Steinbuchel86: Steinbuchel A, Muller M (1986). "Anaerobic pyruvate metabolism of Tritrichomonas foetus and Trichomonas vaginalis hydrogenosomes." Mol Biochem Parasitol 20(1);57-65. PMID: 3090435

Van98: Van Hellemond JJ, Opperdoes FR, Tielens AG (1998). "Trypanosomatidae produce acetate via a mitochondrial acetate:succinate CoA transferase." Proc Natl Acad Sci U S A 95(6);3036-41. PMID: 9501211

vanVugt79: van Vugt F, van der Meer P, van den Bergh SG (1979). "The formation of propionate and acetate as terminal processes in the energy metabolism of the adult liver fluke Fasciola hepatica." Int J Biochem 10(1);11-8. PMID: 421954

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

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Mullins08: Mullins EA, Francois JA, Kappock TJ (2008). "A specialized citric acid cycle requiring succinyl-coenzyme A (CoA):acetate CoA-transferase (AarC) confers acetic acid resistance on the acidophile Acetobacter aceti." J Bacteriol 190(14);4933-40. PMID: 18502856

Sohling93: Sohling B, Gottschalk G (1993). "Purification and characterization of a coenzyme-A-dependent succinate-semialdehyde dehydrogenase from Clostridium kluyveri." Eur J Biochem 212(1);121-7. PMID: 8444151

Tielens10: Tielens AG, van Grinsven KW, Henze K, van Hellemond JJ, Martin W (2010). "Acetate formation in the energy metabolism of parasitic helminths and protists." Int J Parasitol 40(4);387-97. PMID: 20085767

vanGrinsven09: van Grinsven KW, van Hellemond JJ, Tielens AG (2009). "Acetate:succinate CoA-transferase in the anaerobic mitochondria of Fasciola hepatica." Mol Biochem Parasitol 164(1);74-9. PMID: 19103231

vanHellemond03: van Hellemond JJ, van der Klei A, van Weelden SW, Tielens AG (2003). "Biochemical and evolutionary aspects of anaerobically functioning mitochondria." Philos Trans R Soc Lond B Biol Sci 358(1429);205-13; discussion 213-5. PMID: 12594928

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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