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MetaCyc Pathway: pyruvate fermentation to acetate V
Inferred from experiment

Enzyme View:

Pathway diagram: pyruvate fermentation to acetate V

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 EnergyFermentationPyruvate Fermentation

Some taxa known to possess this pathway include : Crithidia fasciculata, Fasciola hepatica, Leishmania infantum, Leishmania mexicana, Phytomonas, Trypanosoma brucei, Trypanosoma cruzi

Expected Taxonomic Range: Euglenozoa, Opisthokonta

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 [Van98].

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).

Superpathways: anaerobic energy metabolism (invertebrates, mitochondrial), superpathway of anaerobic energy metabolism (invertebrates)

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)

Created 01-Aug-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

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

Prichard68: Prichard R, Schofield P (1968). "The metabolism of phosphoenolpyruvate and pyruvate in the adult fluke Fasciola hepatica." Biochim Biophys Acta 170(1);63-76. PMID: 5721923

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

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

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

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

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

Begley96: Begley, T.P. (1996). "The biosynthesis and degradation of thiamin (vitamin B1)." Natural products report.

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

Birney96: Birney M, Um HD, Klein C (1996). "Novel mechanisms of Escherichia coli succinyl-coenzyme A synthetase regulation." J Bacteriol 178(10);2883-9. PMID: 8631677

Birney97: Birney M, Um H, Klein C (1997). "Multiple levels of regulation of Escherichia coli succinyl-CoA synthetase." Arch Biochem Biophys 347(1);103-12. PMID: 9344470

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

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

Bridger68: Bridger WA, Millen WA, Boyer PD (1968). "Substrate synergism and phosphoenzyme formation in catalysis by succinyl coenzyme A synthetase." Biochemistry 7(10);3608-16. PMID: 4878702

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

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

Camp85: Camp, Pamela J, Randall, Douglas D (1985). "Purification and characterization of the pea chloroplast pyruvate dehydrogenase complex." Plant Physiology, 77:571-577.

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

Collier79: Collier GE, Nishimura JS (1979). "Evidence for a second histidine at the active site of succinyl-CoA synthetase from Escherichia coli." J Biol Chem 254(21);10925-30. PMID: 387761

Diaz95a: 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

ElSayed05: El-Sayed NM, Myler PJ, Blandin G, Berriman M, Crabtree J, Aggarwal G, Caler E, Renauld H, Worthey EA, Hertz-Fowler C, Ghedin E, Peacock C, Bartholomeu DC, Haas BJ, Tran AN, Wortman JR, Alsmark UC, Angiuoli S, Anupama A, Badger J, Bringaud F, Cadag E, Carlton JM, Cerqueira GC, Creasy T, Delcher AL, Djikeng A, Embley TM, Hauser C, Ivens AC, Kummerfeld SK, Pereira-Leal JB, Nilsson D, Peterson J, Salzberg SL, Shallom J, Silva JC, Sundaram J, Westenberger S, White O, Melville SE, Donelson JE, Andersson B, Stuart KD, Hall N (2005). "Comparative genomics of trypanosomatid parasitic protozoa." Science 309(5733);404-9. PMID: 16020724

Grinnell69a: 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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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by Pathway Tools version 19.5 (software by SRI International) on Tue May 3, 2016, biocyc13.