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/Assimilation → Carboxylates Degradation → Acetate Formation|
|Generation of Precursor Metabolites and Energy → Fermentation → Acetate 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
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 [Mai96a], 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 acetyl-CoA synthetase (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 [Van98a, 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].
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)
Mai96a: 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
Van98a: 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
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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