If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: tricarboxylic acid cycle, citric acid cycle, Krebs cycle, Szent-Gyorgyi-Krebs cycle, TCA cycle I (2-oxoglutarate dehydrogenase)
|Superclasses:||Generation of Precursor Metabolites and Energy → TCA cycle|
The TCA pathway is a catabolic pathway of aerobic respiration that generates both energy and reducing power. In addition, it is also the first step in generating precursors for biosynthesis. The pathway is very common, and a variation of it exists in practically all aerobic living organisms [Krebs37, Krebs38, Krebs45].
The input to the cycle is acetyl-CoA, an activated form of acetate that is generated by the degradation of carbohydrates, fats and proteins. A common source of acetyl-coA is pyruvate, which is generated by glycolysis and converted to acetyl-CoA by the pyruvate dehydrogenase complex.
In every turn the TCA cycle converts one molecule of acetyl-CoA into two CO2 molecules, reduces a total of four molecules of either NAD+, NADP+, or quinone to NADH, NADPH and quinol, respectively, and phosphorylates one molecule of GDP to GTP.
The reduced molecules of NADH/NADPH/quinol that are formed by the TCA cycle serve as electron donors for oxidative phosphorylation (see for example aerobic respiration I (cytochrome c)). In that process the electrons flow to a terminal acceptor, powering on their way proton pumps that trasport protons across the cytoplasmic or mitochondrial membranes, generating a proton motive force (PMF). As the protons return to their original location, they power ATPase enzymes that phosphorylate ADP molecules to ATP. The total energy gained from the complete breakdown of one molecule of glucose by glycolysis, the TCA cycle, and oxidative phosphorylation equals about 30 ATP molecules in eukaryotes.
The name of the TCA (short for tricarboxylic acid) cycle is derived from the fact that the first step in the pathway is attachment of acetyl-coA to citrate, an acid with three carboxylate groups. The pathway is also known as the citric acid cycle, and as the Szent-Gyorgyi-Krebs cycle (or just the Krebs cycle), named after the scientists who described it.
About This Pathway
This is a common variation of the pathway that occurs in many bacteria and archaea. There are a few small differences between this prokaryotic version of the cycle and the version found in most eukaryotes (see TCA cycle II (plants and fungi)). In this pathway, an NADP-dependent enzyme (EC 184.108.40.206) catalyzes the dehydrogenation of D-threo-isocitrate to 2-oxoglutarate, while eukaryotes employ an NAD+-dependent enzyme (EC 220.127.116.11). Another difference is that while in most eukaryotes the conversion of (S)-malate to oxaloacetate is catalyzed only by an NAD-dependent enzyme (EC 18.104.22.168), prokaryotes that employ this variation of the TCA cycle possess an alternative quinone-dependent enzyme (EC 22.214.171.124).
While the pathway is most common in heterotrophic bacteria and arachaea, there is evidence for its presence in some facultatively autotrophic archaea when growing under heterotrophic conditions.
Variants: TCA cycle II (plants and fungi) , TCA cycle III (animals) , TCA cycle IV (2-oxoglutarate decarboxylase) , TCA cycle V (2-oxoglutarate:ferredoxin oxidoreductase) , TCA cycle VI (obligate autotrophs) , TCA cycle VII (acetate-producers) , TCA cycle VIII (helicobacter)
Nimmo87: Nimmo HG, Borthwick AC, el-Mansi EM, Holms WH, MacKintosh C, Nimmo GA (1987). "Regulation of the enzymes at the branchpoint between the citric acid cycle and the glyoxylate bypass in Escherichia coli." Biochem Soc Symp 1987;54;93-101. PMID: 3333001
Walsh84: Walsh K, Koshland DE (1984). "Determination of flux through the branch point of two metabolic cycles. The tricarboxylic acid cycle and the glyoxylate shunt." J Biol Chem 1984;259(15);9646-54. PMID: 6378912
Walsh87: Walsh K, Schena M, Flint AJ, Koshland DE (1987). "Compensatory regulation in metabolic pathways--responses to increases and decreases in citrate synthase levels." Biochem Soc Symp 1987;54;183-95. PMID: 3332995
Al12: Al Mamun AA, Lombardo MJ, Shee C, Lisewski AM, Gonzalez C, Lin D, Nehring RB, Saint-Ruf C, Gibson JL, Frisch RL, Lichtarge O, Hastings PJ, Rosenberg SM (2012). "Identity and function of a large gene network underlying mutagenic repair of DNA breaks." Science 338(6112);1344-8. PMID: 23224554
Allen64: Allen, S.H., Kellermeyer, R.W., Ssjernholm, R.L., Wood, H.G. (1964). "Purification and properties of enzymes involved in the propionic acid fermentation." J Bacteriol 87;171-87. PMID: 14102852
Anderson88: Anderson DH, Duckworth HW (1988). "In vitro mutagenesis of Escherichia coli citrate synthase to clarify the locations of ligand binding sites." J Biol Chem 1988;263(5);2163-9. PMID: 3276685
Apostolakos82: Apostolakos D, Menter PA, Rampsch BJ, Reeves HC, Birge EA "Genetic map position of the cistron coding for isocitrate dehydrogenase in Escherichia coli K-12." Current Microbiology 1982;7:45-47.
Arifuzzaman06: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699
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
Banerjee05: Banerjee S, Nandyala A, Podili R, Katoch VM, Hasnain SE (2005). "Comparison of Mycobacterium tuberculosis isocitrate dehydrogenases (ICD-1 and ICD-2) reveals differences in coenzyme affinity, oligomeric state, pH tolerance and phylogenetic affiliation." BMC Biochem 6;20. PMID: 16194279
Barker00: Barker HC, Kinsella N, Jaspe A, Friedrich T, O'Connor CD (2000). "Formate protects stationary-phase Escherichia coli and Salmonella cells from killing by a cationic antimicrobial peptide." Mol Microbiol 35(6);1518-29. PMID: 10760151
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.
Berkemeyer98: Berkemeyer M, Scheibe R, Ocheretina O (1998). "A novel, non-redox-regulated NAD-dependent malate dehydrogenase from chloroplasts of Arabidopsis thaliana L." J Biol Chem 273(43);27927-33. PMID: 9774405
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
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