If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
Synonyms: reductive tricarboxylic acid cycle, reductive tricarboxylic acid pathway, reductive citric acid cycle, reverse citric acid cycle, carbon fixation, CO2 fixation, reductive carboxylic acid cycle
|Superclasses:||Degradation/Utilization/Assimilation → C1 Compounds Utilization and Assimilation → CO2 Fixation → Autotrophic CO2 Fixation → Reductive TCA Cycles|
Pathway Summary from MetaCyc:
The reductive tricarboxylic acid (TCA) cycle is a carbon dioxide fixation pathway found in some autotrophic eubacteria and archaea. It is considered to be a primordial pathway for production of starting organic molecules for biosynthesis of sugars, lipids, amino acids, pyrimidines and pyrroles [Smith04, Romano96, Buchanan90]. Other pathways of this type are the Calvin-Benson-Bassham cycle, the reductive acetyl coenzyme A pathway, and the 3-hydroxypropanoate cycle.
The reductive TCA cycle is largely the oxidative, catabolic TCA cycle in reverse. Most of the enzymes of the TCA cycle work reversibly and could catalyze both directions. Only three counteracting enzyme pairs are thought to determine the oxidative or reductive direction of the cycle. These three enzymes are ATP-citrate lyase; 2-oxoglutarate synthase; and fumarate reductase (the names provided here are the names of the enzyme catalyzing the reductive direction) [Schauder87, Shiba85, Siebers04]. It should be noted that these enzymes may participate in other pathways (for example, 2-oxoglutarate synthase also participates in the oxidative TCA cycle found in Helicobacteraceae). Nonetheless, the presence of these enzyme activities in autotrophically grown bacteria and archaea is considered indicative of the presence of the reductive TCA cycle.
pyruvate:ferredoxin oxidoreductase is also a key enzyme in the cycle [Hugler05]. The cycle results in the fixation of two molecules of carbon dioxide in the production of one molecule of acetyl-CoA (in [Hugler05], [Takai05] and [Siebers04]).
About This Pathway
A modified reductive TCA cycle has been found in Hydrogenobacter thermophilus [Shiba85]. There are a few differences between the pathway in this organism and the pathway in Chlorobium limicola, the organism in which the pathway was initially described (see reductive TCA cycle I). One key difference is in the conversion of citrate to oxaloacetate and acetyl-coA. In Chlorobium limicola this reaction is catalyzed by ATP-citrate lyase, an α4β4 complex which is a key enzyme of the pathway. In Hydrogenobacter thermophilus this conversion is catalyzed by two different enzymes. The first enzyme, citryl-CoA synthetase, catalyzes the convcersion of citrate to citryl-coA, while the second enzyme, citryl-coA lyase, catalyzes the splitting of citryl-coA into oxaloacetate and acetyl-coA [Aoshima04a].
A similar difference is the carboxylation of 2-oxoglutarate to D-threo-isocitrate, which in Chlorobium limicola is catalyzed by isocitrate dehydrogenase. Once again, in Hydrogenobacter thermophilus this reaction is catalyzed by two enzymes. The first enzyme, 2-oxoglutarate carboxylase, catalyzes the ATP-dependent carboxylation of 2-oxoglutarate to oxalosuccinate, while the second enzyme catalyzes the NAD-dependent conversion of oxalosuccinate to D-threo-isocitrate [Aoshima06].
Pathway Evidence Glyph:
Key to pathway glyph edge colors:
An enzyme catalyzing this reaction is present in this organism
An enzyme catalyzing this reaction was identified in this organism by the Pathway Hole Filler
No enzyme catalyzing this reaction has been identified in this organism
The reaction and any enzyme that catalyzes it (if one has been identified) is unique to this pathway
Aoshima04a: Aoshima M, Ishii M, Igarashi Y (2004). "A novel enzyme, citryl-CoA lyase, catalysing the second step of the citrate cleavage reaction in Hydrogenobacter thermophilus TK-6." Mol Microbiol 52(3);763-70. PMID: 15101982
Aoshima06: Aoshima M, Igarashi Y (2006). "A novel oxalosuccinate-forming enzyme involved in the reductive carboxylation of 2-oxoglutarate in Hydrogenobacter thermophilus TK-6." Mol Microbiol 62(3);748-59. PMID: 17076668
Hugler05: Hugler M, Wirsen CO, Fuchs G, Taylor CD, Sievert SM (2005). "Evidence for autotrophic CO2 fixation via the reductive tricarboxylic acid cycle by members of the epsilon subdivision of proteobacteria." J Bacteriol 187(9);3020-7. PMID: 15838028
Schauder87: Schauder R, Widdel F, Fuchs G (1987). "Carbon assimilation pathways in sulfate-reducing bacteria II. Enzymes of a reductive citric acid cycle in the autotrophic Desulfobacter hydrogenophilus." Arch Microbiol 148: 218-225.
Selig94: Selig M, Schonheit P (1994). "Oxidation of organic compounds to CO2 with sulfur or thiosulfate as electron acceptor in the anaerobic hyperthermophilic archaea Thermoproteus tenax and Pyrobaculum islandicum proceeds via the citric acid cycle." Arch Microbiol 162: 286-294.
Shiba85: Shiba H, Kawasumi T, Igarashi Y, Kodama T, Minoda Y (1985). "The CO2 assimilation via the reductive tricarboxylic acid cycle in an obligately autotrophic, aerobic hydrogen-oxidizing bacterium, Hydrogenobacter thermophilus." Arch Microbiol 141: 198-203.
Siebers04: Siebers B, Tjaden B, Michalke K, Dorr C, Ahmed H, Zaparty M, Gordon P, Sensen CW, Zibat A, Klenk HP, Schuster SC, Hensel R (2004). "Reconstruction of the central carbohydrate metabolism of Thermoproteus tenax by use of genomic and biochemical data." J Bacteriol 186(7);2179-94. PMID: 15028704
Takai05: Takai K, Campbell BJ, Cary SC, Suzuki M, Oida H, Nunoura T, Hirayama H, Nakagawa S, Suzuki Y, Inagaki F, Horikoshi K (2005). "Enzymatic and genetic characterization of carbon and energy metabolisms by deep-sea hydrothermal chemolithoautotrophic isolates of Epsilonproteobacteria." Appl Environ Microbiol 71(11);7310-20. PMID: 16269773
Fujimoto12: Fujimoto N., Kosaka T., Yamada M. (2012). "Menaquinone as Well as Ubiquinone as a Crucial Component in the Escherichia coli Respiratory Chain." Chapter 10 in Chemical Biology, edited by D Ekinci, ISBN 978-953-51-0049-2.
Park06: Park YJ, Yoo CB, Choi SY, Lee HB (2006). "Purifications and characterizations of a ferredoxin and its related 2-oxoacid:ferredoxin oxidoreductase from the hyperthermophilic archaeon, Sulfolobus solfataricus P1." J Biochem Mol Biol 39(1);46-54. PMID: 16466637
Rubio06: Rubio S, Larson TR, Gonzalez-Guzman M, Alejandro S, Graham IA, Serrano R, Rodriguez PL (2006). "An Arabidopsis mutant impaired in coenzyme A biosynthesis is sugar dependent for seedling establishment." Plant Physiol 140(3);830-43. PMID: 16415216
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