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MetaCyc Pathway: partial TCA cycle (obligate autotrophs)
Inferred from experiment

Pathway diagram: partial TCA cycle (obligate autotrophs)

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Synonyms: TCA cycle VI (obligate autotrophs)

Superclasses: Generation of Precursor Metabolites and EnergyTCA cycle

Some taxa known to possess this pathway include : Acidithiobacillus thiooxidans, Cyanobium gracile PCC 6307, Geminocystis herdmanii PCC 6308, Thiobacillus thioparus

Expected Taxonomic Range: Chroococcales, Prochlorococcaceae, Proteobacteria

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

In obligate autotrophs exogenously furnished organic compounds make a very small contribution to cellular carbon [Smith67a]. In a study conducted with obligate autotrophic Thiobacillus strains, as well as several species of Cyanobacteria, acetate, which was the most readily incorporated compound of those studied, contributed only about 10% of newly synthesized cellular carbon.

The carbon from pyruvate, acetate, and glutamate provided exogenously was incorporated into restricted groups of cellular amino acids. In addition, the enzymes 2-oxoglutarate dehydrogenase or 2-oxoglutarate decarboxylase are missing from the obligate autotrophs that were studied, and activities of malic enzyme and succinate dehydrogenase had extremely low levels.

The authors concluded that the tricarboxylic acid cycle in these organisms is blocked at the level of 2-oxoglutarate oxidation [Smith67a]. A later study showed that while most cyanobacteria do posses the enzymes required for a full TCA cycle (see TCA cycle IV (2-oxoglutarate decarboxylase)), cyanobacteria of the Prochlorococcus and marine Synechococcus genera lack 2-oxoglutarate decarboxylase and thus are likely to operate the pathway described here [Zhang11d].

Variants: superpathway of glyoxylate bypass and TCA, TCA cycle I (prokaryotic), 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 VII (acetate-producers), TCA cycle VIII (helicobacter)

Created 05-May-2008 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

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

Smith67a: Smith AJ, London J, Stanier RY (1967). "Biochemical basis of obligate autotrophy in blue-green algae and thiobacilli." J Bacteriol 94(4);972-83. PMID: 4963789

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

Zhang11d: Zhang, S., Bryant, D. A. (2011). "The tricarboxylic acid cycle in cyanobacteria." Science 334:1551-1553.

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

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

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

Birolo00: Birolo L, Tutino ML, Fontanella B, Gerday C, Mainolfi K, Pascarella S, Sannia G, Vinci F, Marino G (2000). "Aspartate aminotransferase from the Antarctic bacterium Pseudoalteromonas haloplanktis TAC 125. Cloning, expression, properties, and molecular modelling." Eur J Biochem 267(9);2790-802. PMID: 10785402

Blumenthal73: Blumenthal KM, Smith EL (1973). "Nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase of Neurospora. I. Isolation, subunits, amino acid composition, sulfhydryl groups, and identification of a lysine residue reactive with pyridoxal phosphate and N-ethylmaleimide." J Biol Chem 248(17);6002-8. PMID: 4146914

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

Bonete90: Bonete MJ, Camacho ML, Cadenas E (1990). "Analysis of the kinetic mechanism of halophilic NADP-dependent glutamate dehydrogenase." Biochim Biophys Acta 1990;1041(3);305-10. PMID: 1980084

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

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

Bruns76: Bruns GA, Eisenman RE, Gerald PS (1976). "Human mitochondrial NADP-dependent isocitrate dehydrogenase in man-mouse somatic cell hybrids." Cytogenet Cell Genet 17(4);200-11. PMID: 11969

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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, biocyc14.