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.
Synonyms: acetate fermentation, acetate:succinate CoA transferase/SCoAS cycle, ASCT cycle
|Superclasses:||Generation of Precursor Metabolites and Energy → Fermentation → Pyruvate Fermentation|
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 exists in different forms during its life cycle. In the mammalian bloodstream it exists as long, slender-forms, while in the insect it appears as stubby forms known as procyclic cells. Profound differences exist in the metabolism of the two forms.
The long slender bloodstream form depends entirely on glycolysis for energy generation and excretes pyruvate as the major end product of carbohydrate metabolism. In the procyclic stage, the end product of glycolysis, pyruvate, is not excreted but further metabolized inside the mitochondrion. pyruvate enters the mitochondrion and is converted by the pyruvate dehydrogenase complex into acetyl-CoA. This acetyl-CoA is not degraded to carbon dioxide via the TCA cycle I (prokaryotic) (even though these enzymes are present in the organism) [vanWeelden03], but is converted instead into acetate [Riviere04]. Acetate is the main end product of glucose metabolism in a number of other trypanosomatides, such as Leishmania infantum and Leishmania mexicana [Van98a].
Acetate formation is carried out by acetyl:succinate CoA-transferase (ASCT), an enzyme that transfers the CoA group from acetyl-CoA to succinate, producing succinyl-CoA. Since succinyl-CoA can be restored to succinate, the pathway has been named ASCT cycle. 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].
Occurrence of the ASCT cycle in mitochondria is very restricted; it has only been found in trypanosomatid and some parasitic helminths such as Fasciola hepatica [Prichard68, Barrett78, vanVugt79, Saz96].
ASCT is found in several other organisms that do not have mitochondria, including the hydrogenosome-containing trichomonads (such as Tritrichomonas suis and Trichomonas vaginalis [Steinbuchel86]) and the anaerobic fungus Neocallimastix sp. LM-2[MarvinSikkema93]. Since these organisms do not have the pyruvate decarboxylation to acetyl CoA, they use a different pathway (see the pathway pyruvate fermentation to acetate VI).
Subpathways: acetate formation from acetyl-CoA III (succinate)
Variants: pyruvate fermentation to acetate and alanine, pyruvate fermentation to acetate and lactate I, pyruvate fermentation to acetate and lactate II, pyruvate fermentation to acetate I, pyruvate fermentation to acetate II, pyruvate fermentation to acetate III, pyruvate fermentation to acetate IV, pyruvate fermentation to acetate VI, pyruvate fermentation to acetate VII, pyruvate fermentation to acetate VIII, pyruvate fermentation to acetone, pyruvate fermentation to butanoate, pyruvate fermentation to butanol I, pyruvate fermentation to butanol II, pyruvate fermentation to ethanol I, pyruvate fermentation to ethanol II, pyruvate fermentation to ethanol III, pyruvate fermentation to hexanol, pyruvate fermentation to isobutanol (engineered), pyruvate fermentation to lactate, pyruvate fermentation to opines, pyruvate fermentation to propanoate I, pyruvate fermentation to propanoate II (acrylate pathway), superpathway of Clostridium acetobutylicum acidogenic and solventogenic fermentation, superpathway of Clostridium acetobutylicum acidogenic fermentation, superpathway of Clostridium acetobutylicum solventogenic fermentation, superpathway of fermentation (Chlamydomonas reinhardtii)
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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
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
vanWeelden03: van Weelden SW, Fast B, Vogt A, van der Meer P, Saas J, van Hellemond JJ, Tielens AG, Boshart M (2003). "Procyclic Trypanosoma brucei do not use Krebs cycle activity for energy generation." J Biol Chem 278(15);12854-63. PMID: 12562769
Bailey99: Bailey DL, Fraser ME, Bridger WA, James MN, Wolodko WT (1999). "A dimeric form of Escherichia coli succinyl-CoA synthetase produced by site-directed mutagenesis." J Mol Biol 285(4);1655-66. PMID: 9917403
Beh93: Beh M, Strauss G, Huber R, Stetter K-O, Fuchs G (1993). "Enzymes of the reductive citric acid cycle in the autotrophic eubacterium Aquifex pyrophilus and in the archaebacterium Thermoproteus neutrophilus." Arch Microbiol 160: 306-311.
Bild80: Bild GS, Janson CA, Boyer PD (1980). "Subunit interaction during catalysis. ATP modulation of catalytic steps in the succinyl-CoA synthetase reaction." J Biol Chem 255(17);8109-15. PMID: 6997289
BochudAllemann02: Bochud-Allemann N, Schneider A (2002). "Mitochondrial substrate level phosphorylation is essential for growth of procyclic Trypanosoma brucei." J Biol Chem 277(36);32849-54. PMID: 12095995
Buttlaire77: Buttlaire DH, Chon M (1977). "Interactions of phospho- and dephosphosuccinyl coenzyme A synthetase with manganous ion and substrates. Studies of manganese complexes by NMR relaxation rates of water protons." J Biol Chem 252(6);1957-64. PMID: 321448
Camp88: Camp, Pamela J, Miernyk, Jan A, Randall, Douglas D (1988). "Some kinetic and regulatory properties of the pea chloroplast pyruvate dehydrogenase complex." Biochimica et Biophysica Acta, 933:269-275.
Collier78: Collier GE, Nishimura JS (1978). "Affinity labeling of succinyl-CoA synthetase from porcine heart and Escherichia coli with oxidized coenzyme A disulfide." J Biol Chem 253(14);4938-43. PMID: 353044
Diaz95: Diaz F, Komuniecki R (1995). "Pyruvate dehydrogenase complex from the primitive insect trypanosomatid, Crithidia fasciculata: dihydrolipoyl dehydrogenase-binding protein has multiple lipoyl domains." Mol Biochem Parasitol 75(1);87-97. PMID: 8720178
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Grinnell69: Grinnell FL, Nishimura JS (1969). "Succinate thiokinase of Escherichia coli. Purification, phosphorylation of the enzyme, and exchange reactions catalyzed by the enzyme." Biochemistry 8(2);562-8. PMID: 4240087
Harmych02: Harmych S, Arnette R, Komuniecki R (2002). "Role of dihydrolipoyl dehydrogenase (E3) and a novel E3-binding protein in the NADH sensitivity of the pyruvate dehydrogenase complex from anaerobic mitochondria of the parasitic nematode, Ascaris suum." Mol Biochem Parasitol 125(1-2);135-46. PMID: 12467981
Hidber07: Hidber E, Brownie ER, Hayakawa K, Fraser ME (2007). "Participation of Cys123alpha of Escherichia coli succinyl-CoA synthetase in catalysis." Acta Crystallogr D Biol Crystallogr 63(Pt 8);876-84. PMID: 17642514
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