If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
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|
Pathway Summary from MetaCyc:
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 18.104.22.168) catalyzes the dehydrogenation of D-threo-isocitrate to 2-oxoglutarate, while eukaryotes employ an NAD+-dependent enzyme (EC 22.214.171.124). Another difference is that while in most eukaryotes the conversion of (S)-malate to oxaloacetate is catalyzed only by an NAD-dependent enzyme (EC 126.96.36.199), prokaryotes that employ this variation of the TCA cycle possess an alternative quinone-dependent enzyme (EC 188.8.131.52).
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.
Superpathways: superpathway of glyoxylate bypass and TCA
Pathway Evidence Glyph:
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
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