Glyoxylate Cycle

Sonia Beeckmans, Vrije Universiteit Brussel, Sint‐Genesius‐Rode, Belgium

Published online: April 2001

DOI: 10.1038/npg.els.0001370

Some organisms possess enzymes that allow the net conversion of acetyl-CoA to succinate. This is accomplished by a special pathway, the glyoxylate cycle, which may be regarded as an anaplerotic (replenishing) pathway.

Keywords: acetyl-CoA; succinate; glyoxysome; isocitrate lyase; malate synthase; metabolism; enzyme

Figure 1. The central role of acetyl-CoA in overall metabolism. The citric acid cycle, which is an amphibolic pathway, is shown in green. Catabolic pathways are in blue. ATP-requiring steps or pathways are in red. In eukaryotes, different pathways are confined to different organelles (see Table 1).
Figure 2. The glyoxylate cycle (red) and its relationship with the citric acid cycle (blue).
Figure 3. Oxidation steps occurring within plant glyoxysomes. FADH2 is reoxidized with the generation of  H2O2, which is handled by catalase. Possible mechanisms for the reoxidation of NADH are shown (a–c) and are discussed in the text.
Figure 4. The glyoxylate pathway within plants. The classical view of the glyoxylate cycle is shown at the top. Glyoxysomal NADH is reoxidized through some kind of redox system. More recent views on the glyoxylate pathway within plants are shown below. Reoxidation of NADH occurs in the mitochondrial oxidative phosphorylation pathway. This involves a shuttle system and transport of various metabolites. The exact location of aconitase (glyoxysome or cytoplasm?) is still a matter of discussion.
Figure 5. Bifurcation at the level of isocitrate in bacteria. Enzyme activities of isocitrate dehydrogenase (ICDH) and possibly also isocitrate lyase (ICL), which in bacteria occur in the same compartment, are regulated through phosphorylation.
Figure 6. Sequence homologies among isocitrate lyases and malate synthases from plants, fungi, bacteria and invertebrates. Sequence data can be retrieved from GenBank, using the following accession numbers. ICLases. From plants: M83534 (Arabidopsis thaliana); L08482 (Brassica napus); Z35499 (Cucumis sativus); D78256 (Cucurbita maxima); L02329 (Glycine max); X52136 (Gossypium hirsutum); U18678 (Lycopersicon esculentum); M17145 (Ricinus communis). From fungi: X62696 (Aspergillus nidulans); D00703 (Candida tropicalis); JC6182 (Coprinus cinereus); X62697 (Neurospora crassa); X65554 (Saccharomyces cerevisiae); X72848 (Yarrowia lipolytica). From bacteria: U18765 (Chlamydomonas reinhardtii); M22621 (Escherichia coli); Z29367 (Rhodococcus fascians). MSases. From plants: J04468 (Brassica napus); X15425 (Cucumis sativus); X56948 (Cucurbita maxima); L01629 (Glycine max); X52305 (Gossypium hirsutum); X78852 (Raphanus sativus); X52806 (Ricinus communis); L35914 (Zea mays). From fungi: X56671 (Aspergillus nidulans); D13415 (Candida tropicalis); P21360 (Hansenula polymorpha); X56672 (Neurospora crassa); X64407 (Saccharomyces cerevisiae). From bacteria: X12431 (Escherichia coli); U63518 (Streptomyces arenae). The invertebrate bifunctional enzyme (ICLase + MSase): U23159 (Caenorhabditis elegans). Boxes correspond to highly conserved regions; the nine fully conserved tryptophan residues in MSase are indicated with a blue diamond. In ICLase sequences a capital (respectively lower case) letter indicates a conserved amino acid in 16 (respectively 9) out of 18 ICLase sequences. In MSase sequences a capital (respectively lower case) letter indicates a conserved amino acid in 14 (respectively 8) out of 16 MSase sequences. Amino acids known to be involved in ICLase in substrate-binding and/or catalysis are indicated with a red line. In the bifunctional invertebrate enzyme, V8 protease digestion occurs as indicated by green triangles.
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 References
    Beeckmans S (1984) Some structural and regulatory aspects of citrate synthase. International Journal of Biochemistry 16: 341–351.
    Beeckmans S (1999) Chromatographic methods to study protein–protein interactions. Methods (A Companion to Methods in Enzymology) 19: 278–305.
    Beeckmans S, Van Driessche E and Kanarek L (1993) Immobilized enzymes as tools for the demonstration of metabolon formation. A short overview. Journal of Molecular Recognition 6: 195–204.
    Beeckmans S, Khan AS, Kanarek L and Van Driessche E (1994a) Ligand binding on to maize (Zea mays) malate synthase: a structural study. Biochemical Journal 303: 413–421.
    Beeckmans S, Khan AS, Van Driessche E and Kanarek L (1994b) A specific association between the glyoxylic-acid-cycle enzymes isocitrate lyase and malate synthase. European Journal of Biochemistry 224: 197–201.
    Beeckmans S, Khan AS and Van Driessche E (1997) Role of  Mg2+ in the structure and activity of maize (Zea mays L.) isocitrate lyase: indications for hysteretic behaviour. Biochemical Journal 327: 171–176.
    Beevers H (1979) Microbodies in higher plants. Annual Review of Plant Physiology 30: 159–193.
    Breidenbach RW and Beevers H (1967) Association of the glyoxylate cycle enzymes in a novel subcellular particle from castor bean endosperm. Biochemical and Biophysical Research Communications 27: 462–469.
    Britton KL, Langridge SJ, Baker PJ et al. (2000) The crystal structure and active site location of isocitrate lyase from the fungus Aspergillus nidulans. Structure 8: 349–362.
    Cioni M, Pinzauti G and Vanni PL (1981) Comparative biochemistry of the glyoxylate cycle. Comparative Biochemistry and Physiology 70B: 1–26.
    Clegg JS (1984) Properties and metabolism of the aqueous cytoplasm and its boundaries. American Journal of Physiology 246: R133–R151.
    Comai L, Dietrich RA, Maslyar DJ, Badon CS and Harada JJ (1989) Coordinate expression of transcriptionally regulated isocitrate lyase and malate synthase genes in Brassica napus L. Plant Cell 1: 293–300.
    Davis WL and Goodman DB (1992) Evidence for the glyoxylate cycle in human liver. The Anatomical Record 234: 461–468.
    Escher C-L and Widmer F (1997) Lipid mobilization and gluconeogenesis in plants: do glyoxylate cycle enzyme activities constitute a real cycle? A hypothesis. Biological Chemistry 378: 803–813.
    Fernández E, Moreno F and Rodicio R (1992) The ILC1 gene from Saccharomyces cerevisiae. European Journal of Biochemistry 204: 983–990.
    Gancedo JM (1992) Carbon catabolite repression in yeast. European Journal of Biochemistry 206: 297–313.
    Giachetti E, Pinzauti G, Bonaccorsi R, Vincenzini MT and Vanni P (1987) Isocitrate lyase from higher plants. Phytochemistry 26: 2439–2446.
    Giachetti E, Pinzauti G, Bonaccorsi R and Vanni P (1988) Isocitrate lyase: characterization of its true substrate and the role of magnesium ion. European Journal of Biochemistry 172: 85–91.
    Hikida M, Atomi H, Fukuda Y et al. (1991) Presence of two transcribed malate synthase genes in an n-alkane-utilizing yeast, Candida tropicalis. Journal of Biochemistry 110: 909–914.
    Howard BR, Endrizzi JA and Remington SJ (2000) Crystal structure of Escherichia coli malate synthase G complexed with magnesium and glyoxylate at 2.0 Å resolution: mechanistic implications. Biochemistry 39: 3156–3168.
    Huang AH (1992) Oil bodies and oleosins in seeds. Annual Review of Plant Physiology 43: 177–200.
    Khan AS, Van Driessche E, Kanarek L and Beeckmans S (1992) The purification and characterization of maize (Zea mays L.) isocitrate lyase. Archives of Biochemistry and Biophysics 297: 9–18.
    Khan AS, Van Driessche E, Kanarek L and Beeckmans S (1993) Purification of the glyoxylate cycle enzyme malate synthase from maize (Zea mays L.) and characterization of a proteolytic fragment. Protein Expression and Purification 4: 519–528.
    Kornberg HL and Krebs HA (1957) Synthesis of cell constituents from C2-units by a modified tricarboxylic acid cycle. Nature 179: 988–991.
    Liu F, Thatcher JD, Barral JM and Epstein HF (1995) Bifunctional glyoxylate cycle protein of Caenorhabditis elegans: a developmentally regulated protein of intestine and muscle. Developmental Biology 169: 399–414.
    Liu F, Thatcher JD and Epstein HF (1997) Induction of glyoxylate cycle expression in Caenorhabditis elegans: a fasting response throughout larval development. Biochemistry 36: 255–260.
    McNew JA and Goodman JM (1996) The targeting and assembly of peroxisomal proteins: some old rules do not apply. Trends in Biological Sciences 21: 54–58.
    Mullen RT and Trelease RN (1996) Biogenesis and membrane properties of peroxisomes: does the boundary membrane serve and protect? Trends in Plant Science 1: 389–394.
    Nimmo HG (1984) Control of Escherichia coli isocitrate dehydrogenase: an example of protein phosphorylation in a prokaryote. Trends in Biological Sciences 9: 475–478.
    Popov VN, Igamberdiev AU, Schnarrenberger C and Volvenkin SV (1996) Induction of glyoxylate cycle enzymes in rat liver upon food starvation. FEBS Letters 390: 258–260.
    Saier MH (1989) Protein phosphorylation and allosteric control of inducer exclusion and catabolite repression by the bacterial phosphoenolpyruvate:sugar phosphotransferase system. Microbiology Reviews 53: 109–120.
    Sharma V, Sarma S, Hoener zu Bentrup K et al. (2000) Structure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis. Nature Structural Biology 7: 663–668.
    Srere PA (1987) Complexes of sequential metabolic enzymes. Annual Review of Biochemistry 56: 89–124.
    Srivastava DK and Bernhard SA (1986) Enzyme–enzyme interactions and the regulation of metabolic reaction pathways. Current Topics in Cellular Regulation 28: 1–68.
    Tolbert NE (1971) Microbodies–peroxisomes and glyoxysomes. Annual Review of Plant Physiology 22: 45–71.
    Turley RB and Trelease RN (1990) Development and regulation of the glyoxysomal enzymes during cotton seed maturation and growth. Plant Molecular Biology 14: 137–146.
    Ullmann A (1985) Catabolite repression. Biochimie 67: 29–34.
    Van Driessche E, Beeckmans S, Dejaegere R and Kanarek L (1984) Thiourea: the anti-oxidant of choice for the purification of proteins from phenol-rich plant tissues. Analytical Biochemistry 141: 184–188.
    Vanni P, Giachetti E, Pinzauti G and McFadden BA (1990) Comparative structure, function and regulation of isocitrate lyase, an important assimilatory enzyme. Comparative Biochemistry and Physiology 95B: 431–458.
    Wiemer EAC, Terlecky SR, Nuttley WM and Subramani S (1995) Characterization of yeast and human receptors for the carboxy-terminal tripeptide peroxisomal targeting signal. Cold Spring Harbour Symposia on Quantitative Biology; Protein Kinesis LX: 637–648.

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Article Title: Glyoxylate Cycle
 
How to Cite close
Beeckmans, Sonia(Apr 2001) Glyoxylate Cycle. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0001370]