MetaCyc Pathway: TCA cycle II (plants and fungi)
Inferred from experiment

Enzyme View:

Pathway diagram: TCA cycle II (plants and fungi)

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: TCA cycle -- aerobic respiration, tricarboxylic acid cycle, citric acid cycle, Szent-Gyorgyi-Krebs cycle, Krebs cycle

Superclasses: Generation of Precursor Metabolites and EnergyTCA cycle

Some taxa known to possess this pathway include : Arabidopsis thaliana col, Glycine max, Saccharomyces cerevisiae, Vigna radiata radiata

Expected Taxonomic Range: Fungi, Viridiplantae

General Background

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 transport 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.

Some organisms possess a truncated version of the TCA cycle, known as the glyoxylate cycle, that converts acetyl-CoA to biosynthetic intermediates without the loss of CO2 [Walsh84, Nimmo87, Holms87].

About This Pathway

One of the main differences between the eukaryotic TCA cycles (described in this pathway and in TCA cycle III (animals)) and the prokaryotic pathway is that the latter contains an alternative route between (S)-malate and oxaloacetate, catalyzed by EC, malate dehydrogenase (quinone). That enzyme is found in some bacteria, but is absent from most eukaryotes, in which the reaction is catalyzed only by the NAD+-dependent malate dehydrogenase, EC

Another difference concerns the enzyme isocitrate dehydrogenase. Most prokaryotes possess only an NADP+-dependent form ( EC, isocitrate dehydrogenase (NADP+)), which supports both respiration via the TCA cycle and glutamate biosynthesis for anabolic reactions. Eukaryotes, on the other hand, have two types of the enzyme - an NADP+-dependent forms (EC and NAD+-dependent forms (EC It has been shown that the NADP+-dependent enzymes are involved primarily in glutamate biosynthesis, while the NAD+-dependent enzymes are those involved in the TCA cycle [Keys90]. It should be noted that while rare, NAD+-dependent isocitrate dehydrogenases are also found in bacteria that lack the glyoxylate bypass, and thus are missing the enzyme isocitrate lyase [Zhu05]. Examples for prokaryotes that contain an NAD-dependent enzyme include Acidithiobacillus thiooxidans [Inoue02] and Zymomonas mobilis [Wang12c].

The only difference between this pathway, found in plants and fungi, and TCA cycle III (animals), which is found in animals, is the step between succinyl-CoA and succinate. While plants and fungi only use EC, succinate—CoA ligase (ADP-forming), animals also use EC, succinate—CoA ligase (GDP-forming).

Superpathways: superpathway of cytosolic glycolysis (plants), pyruvate dehydrogenase and TCA cycle

Variants: partial TCA cycle (obligate autotrophs), superpathway of glyoxylate bypass and TCA, TCA cycle I (prokaryotic), TCA cycle III (animals), TCA cycle IV (2-oxoglutarate decarboxylase), TCA cycle V (2-oxoglutarate:ferredoxin oxidoreductase), TCA cycle VII (acetate-producers), TCA cycle VIII (helicobacter)

Created 29-Oct-2007 by Caspi R, SRI International


Holms87: Holms WH (1987). "Control of flux through the citric acid cycle and the glyoxylate bypass in Escherichia coli." Biochem Soc Symp 1987;54;17-31. PMID: 3332993

Inoue02: Inoue H, Tamura T, Ehara N, Nishito A, Nakayama Y, Maekawa M, Imada K, Tanaka H, Inagaki K (2002). "Biochemical and molecular characterization of the NAD(+)-dependent isocitrate dehydrogenase from the chemolithotroph Acidithiobacillus thiooxidans." FEMS Microbiol Lett 214(1);127-32. PMID: 12204383

Keys90: Keys DA, McAlister-Henn L (1990). "Subunit structure, expression, and function of NAD(H)-specific isocitrate dehydrogenase in Saccharomyces cerevisiae." J Bacteriol 172(8);4280-7. PMID: 2198251

Krebs37: Krebs HA, Johnson WA (1937). "Acetopyruvic acid (αγ-diketovaleric acid) as an intermediate metabolite in animal tissues." Biochem J 31(5);772-9. PMID: 16746397

Krebs38: Krebs HA, Salvin E, Johnson WA (1938). "The formation of citric and α-ketoglutaric acids in the mammalian body." Biochem J 32(1);113-7. PMID: 16746585

Krebs45: Krebs HA, Eggleston LV (1945). "Metabolism of acetoacetate in animal tissues. 1." Biochem J 39(5);408-19. PMID: 16747930

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

Wang12c: Wang P, Jin M, Zhu G (2012). "Biochemical and molecular characterization of NAD(+)-dependent isocitrate dehydrogenase from the ethanologenic bacterium Zymomonas mobilis." FEMS Microbiol Lett 327(2);134-41. PMID: 22117777

Zhu05: Zhu G, Golding GB, Dean AM (2005). "The selective cause of an ancient adaptation." Science 307(5713);1279-82. PMID: 15653464

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

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

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.

Bennett95: Bennett B, Gruer MJ, Guest JR, Thomson AJ (1995). "Spectroscopic characterisation of an aconitase (AcnA) of Escherichia coli." Eur J Biochem 233(1);317-26. PMID: 7588761

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

Bernstein78: Bernstein LH, Grisham MB, Cole KD, Everse J (1978). "Substrate inhibition of the mitochondrial and cytoplasmic malate dehydrogenases." J Biol Chem 253(24);8697-701. PMID: 214429

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

Bonnarme95: Bonnarme P, Gillet B, Sepulchre AM, Role C, Beloeil JC, Ducrocq C (1995). "Itaconate biosynthesis in Aspergillus terreus." J Bacteriol 177(12);3573-8. PMID: 7768868

Bradbury96: Bradbury AJ, Gruer MJ, Rudd KE, Guest JR (1996). "The second aconitase (AcnB) of Escherichia coli." Microbiology 142 ( Pt 2);389-400. PMID: 8932712

Brandsch89: Brandsch R, Bichler V (1989). "Covalent cofactor binding to flavoenzymes requires specific effectors." Eur J Biochem 1989;182(1);125-8. PMID: 2659351

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

Burke82: Burke JJ, Siedow JN, Moreland DE (1982). "Succinate Dehydrogenase : A Partial Purification from Mung Bean Hypocotyls and Soybean Cotyledons." Plant Physiol 70(6);1577-1581. PMID: 16662722

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

Chistoserdova03: Chistoserdova L, Chen SW, Lapidus A, Lidstrom ME (2003). "Methylotrophy in Methylobacterium extorquens AM1 from a genomic point of view." J Bacteriol 185(10);2980-7. PMID: 12730156

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

Showing only 20 references. To show more, press the button "Show all references".

Report Errors or Provide Feedback
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 20.0 (software by SRI International) on Thu May 5, 2016, BIOCYC12.