α-ketoglutarate dehydrogenase complex

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The α-ketoglutarate dehydrogenase complex (OGDC) is a protein complex in eukaryotes and some bacteria that catalyzes the oxidative decarboxylation of α-ketoglutarate and the subsequent conversion with coenzyme A to succinyl-CoA . This reaction is part of the citric acid cycle . The overall response is:

Ketoglutarate+ CoA -SH + NAD + + CO 2 + NADH Succinyl-CoA

construction

Comparison of OGDC and PDC
OGDC subunits Subunits PDC
α-ketoglutarate dehydrogenase (E 1 ) Pyruvate dehydrogenase (E 1 )
Dihydrolipoamide succinyl transferase (E 2 ) Dihydrolipoyl transacetylase (E 2 )
Dihydrolipamide dehydrogenase (E 3 ) Dihydrolipoyl dehydrogenase (E 3 )

Three enzymes are involved in the α-ketoglutarate dehydrogenase complex: the α-ketoglutarate dehydrogenase E1 subunit ( A , EC  1.2.4.2 ), the dihydrolipoamide succinyl transferase ( B , EC  2.3.1.61 ) and the dihydrolipoamide dehydrogenase ( C. - E , EC  1.8.1.4 ). The complex thus has a structure similar to that of the pyruvate dehydrogenase complex (PDC).

The α-ketoglutarate dehydrogenase, together with the pyruvate dehydrogenase and the branched chain -α-keto acid dehydrogenase, form a family of multi-enzyme complexes known as α-keto acid dehydrogenases.

In the active multienzyme complex, the succinyltransferase is aggregated to form highly symmetrical multimers (tetracosamer of point group 432 , hexacontamer of point group 532) to which the various dehydrogenases are bound.

In eukaryotes, a single variant of the complex has been identified in mitochondria.

reaction

Reaction mechanism, for α-ketoglutarate is R = CH 2 –COO -

OGDC and PDC use the same coenzymes and also catalyze an analogous reaction; the reaction mechanism is also very similar for both complexes. α-Ketoglutarate is oxidatively decarboxylated to succinyl-CoA, producing NADH. In the citric acid cycle, this is fed into the respiratory chain and is used to generate energy.

Formation of succinate in prokaryotes

Modified citric acid cycle metabolic pathways in which a partial step is missing are the norm in bacteria (13 of 17 examined). The missing step may or may not be replaced by other reaction steps. In fact, only three types of bacteria are known to have ketoglutarate dehydrogenase (KDH) activity: Euglena gracilis , Bacillus japonicum and Escherichia coli .- The bacterium Escherichia coli runs the complete citric acid cycle under aerobic conditions as described. In anaerobic conditions it is able to deactivate the KDH. The metabolic pathways that previously formed a circle are now linked like a tree. M. tuberculosis, on the other hand, can switch between two different citric acid cycles, both of which are different from the eukaryotic pathway.

Archaea , but also some bacteria such as Helicobacter pylori , which grows under microaerophilic conditions, catalyze the conversion of α-ketoglutarate to succinyl-CoA by means of an oxidation-sensitive 2-oxoglutarate: ferredoxin oxidoreductase (OGOR, EC  1.2.7.3 ). In contrast to the OGDC, this one contains iron-sulfur clusters ; the flavin and lipoic acid amide are missing. Ferredoxin is used as a reducing agent instead of NADH . Also Mycobacterium tuberculosis contains a CoA-dependent enzyme that, however, is stable even under aerobic conditions.

In various mycobacteria (including Mycobacterium tuberculosis ), the E1 subunit of ketoglutarate dehydrogenase has been replaced by a ketoglutarate decarboxylase, which, independently of coenzyme A, initially produces succinate semialdehyde, which is converted from an NADP + -dependent succinate semialdehyde to succinate dehydrogenase becoming dehydrated.

literature

  • Bunik VI, Fernie AR: Metabolic control exerted by the 2-oxoglutarate dehydrogenase reaction: a cross-kingdom comparison of the crossroad between energy production and nitrogen assimilation . In: Biochem. J. . 422, No. 3, September 2009, pp. 405-21. doi : 10.1042 / BJ20090722 . PMID 19698086 .
  • Kabysheva MS, Storozhevykh TP, Pinelis VG, Bunik VI: Synthetic regulators of the 2-oxoglutarate oxidative decarboxylation alleviate the glutamate excitotoxicity in cerebellar granule neurons . In: Biochem. Pharmacol. . 77, No. 9, May 2009, pp. 1531-40. doi : 10.1016 / j.bcp.2009.02.001 . PMID 19426691 .
  • Bunik VI, Raddatz G, Wanders RJ, Reiser G: Brain pyruvate and 2-oxoglutarate dehydrogenase complexes are mitochondrial targets of the CoA ester of the Refsum disease marker phytanic acid . In: FEBS Lett . 580, No. 14, June 2006, pp. 3551-7. doi : 10.1016 / j.febslet.2006.05.040 . PMID 16737698 .

Individual evidence

  1. ↑ JE Knapp, D. Caroll, JE Lawson, SR Ernst, LJ Reed, ML Hackert: Experssion, purification, and structural analysis of the trimeric form of the catalytic domain of the Escherichia coli dihydroliponamide succinyltransferase. In: Protein Sci. 9, pp. 37-48, 2000
  2. ^ A b H. Robert Horton, Laurence A. Moran, K. Gray Scrimgeour, Marc D. Perry, J. David Rawn and Carsten Biele (translator): Biochemie . Pearson Studies; 4th updated edition 2008; ISBN 978-3-8273-7312-0 ; P. 536
  3. ^ RN Perham: Swinging Arms and Swinging Domains in Multifunctional Enzymes: Catalytic Machines for Multistep Reaction. In: Annu. Rev. Biochem. 69, pp. 961-1004, 2000
  4. ↑ Cordwell SJ: Microbial genomes and "missing" enzymes: redefining biochemical pathways . In: Arch. Microbiol. . 172, No. 5, November 1999, pp. 269-79. PMID 10550468 .
  5. ↑ Mai, X. and Adams, MW. (1996): Characterization of a fourth type of 2-keto acid-oxidizing enzyme from a hyperthermophilic archaeon: 2-ketoglutarate ferredoxin oxidoreductase from Thermococcus litoralis . In: Journal of bacteriology. Volume 178, Number 20, October 1996, pp. 5890-5896, PMID 8830683 , PMC 178443 (free full text).
  6. ↑ Pitson SM, Mendz GL, Srinivasan S, Hazell SL: The tricarboxylic acid cycle of Helicobacter pylori . In: Eur J Biochem . 260, No. 1, February 1999, pp. 258-67. PMID 10091606 .
  7. ↑ Baughn AD, Garforth SJ, Vilchèze C, Jacobs WR: An anaerobic-type alpha-ketoglutarate ferredoxin oxidoreductase completes the oxidative tricarboxylic acid cycle of Mycobacterium tuberculosis . In: PLoS Pathog . . 5, No. 11, November 2009, p. E1000662. doi : 10.1371 / journal.ppat.1000662 . PMID 19936047 . PMC 2773412 (free full text).
  8. ↑ Tian J, Bryk R, Itoh M, Suematsu M, Nathan C: Variant tricarboxylic acid cycle in Mycobacterium tuberculosis: identification of alpha-ketoglutarate decarboxylase . In: Proc. Natl. Acad. Sci. USA . 102, No. 30, July 2005, pp. 10670-5. doi : 10.1073 / pnas.0501605102 . PMID 16027371 . PMC 1180764 (free full text).

Web links

Wikibooks: α-Ketoglutarate Dehydrogenase  - Learning and Teaching Materials