Glyoxylate cycle

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The glyoxylate cycle is a pathway of the synthesis of C 4 - carbohydrates from two molecules of acetyl-CoA possible. A succinate molecule is thus formed during a complete cycle . It is similar to the citric acid cycle and occurs in plants , fungi , many bacteria and some invertebrates , but not in vertebrates . The metabolic pathway is also known as the Krebs-Kornberg cycle or the Krebs-Kornberg-Beevers cycle after its discoverers Hans Adolf Krebs , Hans Leo Kornberg and Harry Beevers .

Alternative metabolic pathways for the assimilation of acetate are the ethylmalonyl-CoA pathway and the methylaspartate cycle .

biochemistry

The glyoxylate cycle in a general scheme. The number of carbon atoms of each metabolite has been highlighted. Please see text for details.

As in the citric acid cycle, the glyoxylate cycle begins with the condensation of a molecule of acetyl-CoA with oxaloacetate , creating citrate . This reaction is catalyzed by a citrate synthase. The citrate is converted into isocitrate by an aconitase .

The catalyzed reactions of isocitrate lyase and malate synthase in detail.

The decarboxylation steps of the citric acid cycle are now circumvented by two subsequent reactions . On the one hand, an isocitrate lyase ( EC  4.1.3.1 ) catalyzes the cleavage of the isocitrate to succinate and glyoxylate . This is then condensed to malate by a malate synthase ( EC  2.3.3.9 ) with another molecule of acetyl CoA. Since the CoA thioester is hydrolyzed, this reaction is irreversible. The circle closes when the malate is oxidized to oxaloacetate by a malate dehydrogenase , which also produces NADH .

The net response for converting two molecules of acetyl-CoA to succinate is:

Since the succinate released can be fed into the citric acid cycle, the glyoxylate cycle is an example of an anaplerotic reaction .

regulation

The sub-steps of the glyoxylate cycle take place in plants in the glyoxysome, in the cytosol and in the mitochondrion. The number of carbon atoms of each metabolite has been highlighted. Please see text for details.

In plants, the reaction is compartmentalized . The majority of the reactions are localized in specialized peroxisomes called glyoxysomes. However, the citrate formed is brought into the cytosol and converted there into isocitrate by a cytosolic aconitase. This is transported back into the glyoxysome, where it enters the glyoxylate cycle. The succinate formed is finally transported to a mitochondrion and can flow into the citric acid cycle there.

In microorganisms, the citric acid cycle does not take place in separate cell compartments, but in the cytoplasm . As a result, the citrate and glyoxylate cycles overlap and need to be regulated.

The change from the citric acid cycle to the glyoxylate cycle includes a switching process on the isocitrate dehydrogenase (IDH, for Escherichia coli EC  1.1.1.42 ). This enzyme catalyzes the oxidative decarboxylation of isocitrate into α-ketoglutarate in the citric acid cycle . Normally the activity of isocitrate dehydrogenase dominates, and thus the reaction sequence of the citric acid cycle. The result is the generation of ATP . If there is a lack of carbohydrates, however, isocitrate should be broken down for the glyoxylate cycle and carbohydrates should be built up. In this case, the IDH must be inactivated and the isocitrate lyase (IL) stimulated.

This is done by phosphorylation of the IDH on a serine residue , which is catalyzed by a protein kinase. This was the first example of an interconvertible enzyme in E. coli in 1989 .

This modification can be reversed by a phosphoprotein phosphatase, so that the IDH regains its activity. This phosphatase is stimulated when the ATP level is low and by intermediate products of glycolysis and the citric acid cycle, while the IC lyase is allosterically inhibited as a result.

Biological importance

The succinate formed is converted into oxaloacetate. This can be converted into phosphoenolpyruvate , which catalyzes a phosphoenolpyruvate carboxykinase . Phosphoenolpyruvate is built up to glucose in the course of gluconeogenesis . As a result, the glyoxylate cycle enables microorganisms to grow with acetate or acetyl-CoA, which has been generated or broken down from various organic compounds ( alkanes , isoprene , alcohols , polyhydroxyalkanoate , acetic acid , triglycerides ).

In plants, the seedling uses the metabolic pathway to generate energy and especially carbohydrates (e.g. sucrose ) for cell growth from stored triglycerides (storage fats). The seedling uses special fat reservoirs, so-called oleosomes , to hydrolyze the triglycerides into fatty acids and glycerine . Glycerine is converted into glyceraldehyde-3-phosphate and can then be further metabolized. The fatty acids get into the glyoxisome and are broken down into acetyl-CoA in the course of β-oxidation . Acetyl-CoA then flows into the glyoxylate cycle. The succinate formed there is finally converted into glucose in the course of gluconeogenesis and can then be further processed into sucrose. Alternatively, succinate can be used in the citric acid cycle to generate energy before photosynthesis of the seedling begins. In plants, the glyoxylate cycle can also be used for the indirect transport of lipids. Plants cannot transport lipids as carriers of chemical energy or as building materials. The glyoxylate cycle transforms these into a transportable, water-soluble form (sucrose) and then converts them back into lipids at their destination.

Since humans (and other vertebrates) lack the two enzymes isocitrate lyase and malate synthase, the acetyl-CoA formed can either build up into fats or breathe in during the citric acid cycle . As a result, on a zero diet , a person can not generate carbohydrates from their fat reserves and must (of necessity) obtain them from amino acids . That is why muscles are broken down with this form of diet.

Alternative to the glyoxylate cycle

Some microorganisms growing on acetate do not have or lack active isocitrate lyase. However, it has been shown that they use alternative metabolic pathways, for example the ethylmalonyl-CoA pathway . This is the case, for example, for Rhodobacter sphaeroides , Methylobacterium extorquens and other representatives of the non-sulfur purple bacteria and Alphaproteobacteria . In the linear metabolic pathway, two reaction steps are required for the conversion of glyoxylate and acetyl-CoA to malate.

In some halobacteria , for example in Haloarcula marismortui , the methyl aspartate cycle operates . A total of nine reaction steps are required to convert isocitrate to succinate. This creates the eponymous methyl aspartate, an unusual, non-proteinogenic amino acid .

literature

  • Georg Fuchs (ed.), Hans. G. Schlegel (Author): General Microbiology. 8th edition. Thieme Verlag, Stuttgart 2007, ISBN 978-3-13-444608-1 , pp. 225f.
  • Katharina Munk (Ed.): Pocket textbook Biology: Microbiology . Thieme Verlag, Stuttgart 2008, ISBN 978-3-13-144861-3 , pp. 405f.
  • Philipp Christen, Rolf Jaussi: Biochemistry: An introduction with 40 learning units . Springer Verlag, Berlin 2004, ISBN 3-540-21164-0 , p. 327f.
  • Jeremy M. Berg, Lubert Stryer, John L. Tymoczko: Biochemistry. 6th edition. Spektrum Akademischer Verlag, 2007, ISBN 978-3-8274-1800-5 , pp. 553f.
  • Michael T. Madigan, John M. Martinko, Jack Parker, Thomas D. Brock: Microbiology . Spektrum Akademischer Verlag, 2003, ISBN 3-8274-0566-1 , p. 700.

Individual evidence

  1. ^ A b S. A. Ensign: Revisiting the glyoxylate cycle: alternate pathways for microbial acetate assimilation. In: Mol Microbiol. 61 (2), 2006, pp. 274-276. PMID 16856935 .
  2. ^ HL Kornberg, HA Krebs (1957): Synthesis of cell constituents from C2 units by a modified tricarboxylic acid cycle. In: Nature . 179 (4568), 1957, pp. 988-991. PMID 13430766 ; doi: 10.1038 / 179988a0 .
  3. ↑ HL Kornberg, H. Beevers: The glyoxylate cycle as a stage in the conversion of fat to carbohydrate in castor beans. In: Biochim Biophys Acta . 26 (3), 1957, pp. 531-537. PMID 13499412 .
  4. ↑ JH Hurley et al .: Structure of a bacterial enzyme regulated by phosphorylation, isocitrate dehydrogenase. In: PNAS . 86 (22), 1989, pp. 8635-8639. PMID 2682654 ; PDF (free full text access).
  5. ^ David Nelson, Michael Cox: Lehninger Biochemie. 4th, completely revised u. exp. Edition. Springer, Berlin 2009, ISBN 978-3-540-68637-8 , p. 846.
  6. ↑ a b T. J. Erb, G. Fuchs, BE Alber: (2S) -Methylsuccinyl-CoA dehydrogenase closes the ethylmalonyl-CoA pathway for acetyl-CoA assimilation. In: Mol Microbiol. 73 (6), 2009, pp. 992-1008. PMID 19703103 ; doi: 10.1111 / j.1365-2958.2009.06837.x .
  7. ↑ M. Khomyakova, Ö. Bükmez, LK Thomas, TJ Erb, IA Berg: A methylaspartate cycle in haloarchaea. In: Science. 331 (6015), 2011, pp. 334-337. PMID 21252347 , doi: 10.1126 / science.1196544 .

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