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MetaCyc Pathway: glyoxylate cycle
Inferred from experiment

Enzyme View:

Pathway diagram: glyoxylate cycle

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: glyoxylate bypass, glyoxylate shunt

Superclasses: Generation of Precursor Metabolites and Energy

Some taxa known to possess this pathway include : Arabidopsis thaliana col, Escherichia coli K-12 substr. MG1655, Haloferax volcanii

Expected Taxonomic Range: Archaea, Bacteria , Eukaryota

The glyoxylate cycle is a sequence of anaplerotic reactions (reactions that form metabolic intermediates for biosynthesis) that enables an organism to use substrates that enter central carbon metabolism at the level of acetyl-CoA as the sole carbon source. Such substrates include fatty acids, alcohols, and esters (often the products of fermentation), as well as waxes, alkenes, and methylated compounds. The pathway does not occur in vertebrates, but it is found in plants and certain bacteria, fungi, and invertebrates.

The pathway is essentially a modified version of the TCA cycle I (prokaryotic) that bypasses those steps in the cycle that lead to a loss of CO2. Acetyl-CoA enters the cycle at two steps, but no carbon escapes it in the form of CO2.

The glyoxylate cycle uses a two-step bypass. One key enzyme, isocitrate lyase (EC, converts D-threo-isocitrate to form succinate and glyoxylate. A second key enzyme, malate synthase (EC, condenses glyoxylate and a second molecule of acetyl-CoA to form (S)-malate. The subsequent oxidation of malate regenerates the initial acetyl-CoA acceptor molecule of the TCA cycle, oxaloacetate. Thus, the succinate that was formed by isocitrate lyase (EC can be withdrawn from the cycle and used for cell carbon biosynthesis.

The pathway was originally discovered in bacteria [Kornberg57], but later was found to operate in some eukaryotic organisms as well. In plants the cycle is invovled in the metabolism of storage oils during germination of seeds [Brownleader97]. The cycle also operates in developing eggs of nematodes, where it converts triacylglycerols to carbohydrates [Patel78].

In Escherichia coli the pathway is active when growth on 2 carbon compounds requires conservation of 4 carbon TCA intermediates. Two acetyl-CoA are taken up per turn. The glyoxylate cycle is repressed during growth on glucose and induced by growth on acetate [Cortay89, Walsh84, LaPorte84, Nimmo84].

It should be notes that some organisms possess alternative pathways that convert acetyl-CoA to 4 carbon biosynthetic intermediates, such as the ethylmalonyl-CoA pathway and the methylaspartate cycle.

Citations: [Eastmond01, Brownleader97a]

Superpathways: superpathway of glycolysis, pyruvate dehydrogenase, TCA, and glyoxylate bypass, superpathway of glyoxylate bypass and TCA, superpathway of glyoxylate cycle and fatty acid degradation


Revised 04-Dec-2007 by Caspi R, SRI International


Brownleader97: Brownleader, M.D., Harborne, J.B., Dey, P.M. (1997). "Carbohydrate metabolism: primary metabolism of monosaccharides." Plant Biochemistry, Eds Dey & Harborne, Academic Press, Harcourt Brace & Co, Publishers, London.

Brownleader97a: Brownleader, M.D., Harborne, J.B., Dey, P.M. (1997). "Carbohydrate metabolism: primary metabolism of monosaccharides." Plant Biochemistry, Eds Dey & Harborne, Academic Press, Harcourt Brace & Co, Publishers, London.

Cortay89: Cortay JC, Bleicher F, Duclos B, Cenatiempo Y, Gautier C, Prato JL, Cozzone AJ (1989). "Utilization of acetate in Escherichia coli: structural organization and differential expression of the ace operon." Biochimie 71(9-10):1043-1049. PMID: 2512996

Eastmond01: Eastmond PJ, Graham IA (2001). "Re-examining the role of the glyoxylate cycle in oilseeds." Trends Plant Sci 2001;6(2);72-8. PMID: 11173291

Kornberg57: Kornberg, HL, Krebs, HA (1957). "Synthesis of cell constituents from C2-units by a modified tricarboxylic acid cycle." Nature 179(4568);988-91. PMID: 13430766

LaPorte84: LaPorte DC, Walsh K, Koshland DE (1984). "The branch point effect. Ultrasensitivity and subsensitivity to metabolic control." J Biol Chem 1984;259(22);14068-75. PMID: 6389540

Nimmo84: Nimmo GA, Nimmo HG (1984). "The regulatory properties of isocitrate dehydrogenase kinase and isocitrate dehydrogenase phosphatase from Escherichia coli ML308 and the roles of these activities in the control of isocitrate dehydrogenase." Eur J Biochem 1984;141(2);409-14. PMID: 6329757

Patel78: Patel TR, McFadden BA (1978). "Caenorhabditis elegans and Ascaris suum: fragmentation of isocitrate lyase in crude extracts." Exp Parasitol 44(1);72-81. PMID: 627278

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

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

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

Amarneh05: Amarneh B, Vik SB (2005). "Direct transfer of NADH from malate dehydrogenase to complex I in Escherichia coli." Cell Biochem Biophys 42(3);251-61. PMID: 15976458

ANALYSISREFEREN: Computational analysis, http://www.arabidopsis.org/servlets/TairObject?type=analysisreference&id=501719615.

Anderson88a: 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

Anstrom03: Anstrom DM, Kallio K, Remington SJ (2003). "Structure of the Escherichia coli malate synthase G:pyruvate:acetyl-coenzyme A abortive ternary complex at 1.95 A resolution." Protein Sci 12(9);1822-32. PMID: 12930982

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

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.

Brock02: Brock M, Maerker C, Schutz A, Volker U, Buckel W (2002). "Oxidation of propionate to pyruvate in Escherichia coli. Involvement of methylcitrate dehydratase and aconitase." Eur J Biochem 269(24);6184-94. PMID: 12473114

Calderon09: Calderon IL, Elias AO, Fuentes EL, Pradenas GA, Castro ME, Arenas FA, Perez JM, Vasquez CC (2009). "Tellurite-mediated disabling of [4Fe-4S] clusters of Escherichia coli dehydratases." Microbiology 155(Pt 6);1840-6. PMID: 19383690

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

Comai89: Comai L, Baden CS, Harada JJ (1989). "Deduced sequence of a malate synthase polypeptide encoded by a subclass of the gene family." J Biol Chem 264(5);2778-82. PMID: 2914930

COMMUNICATION: communication, http://arabidopsis.org/servlets/TairObject?accession=Communication:1675001.

Cornah04: Cornah JE, Germain V, Ward JL, Beale MH, Smith SM (2004). "Lipid utilization, gluconeogenesis, and seedling growth in Arabidopsis mutants lacking the glyoxylate cycle enzyme malate synthase." J Biol Chem 279(41);42916-23. PMID: 15272001

Courtright70: Courtright JB, Henning U (1970). "Malate dehydrogenase mutants in Escherichia coli K-12." J Bacteriol 102(3);722-8. PMID: 4914076

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

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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 Mon May 2, 2016, biocyc14.