Succinyl-CoA synthetases

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Model of the SCS heterodimer (alpha blue, beta yellow) from domestic pigs ( Sus scrofa ) with GTP: potassium as calottes according to PDB 2FP4

Succinyl-CoA synthetases (SCS) (also: succinate-CoA ligases ) are enzyme complexes of the citric acid cycle in all living things. The SCS catalyze a reaction equilibrium between succinate and coenzyme A on the one hand and succinyl-CoA with consumption / gain of the energy-rich GTP ( EC  6.2.1.4 ) or ATP ( EC  6.2.1.5 ) on the other hand.

The simplified reaction equation of this equilibrium is:

Succinyl-CoA+ ADP / GDP + Pi + ATP / GTP + CoA -SH Succinate

The energy of the splitting of the succinyl-CoA is used for the formation of GTP / ATP. In the citric acid cycle, the reaction proceeds from left to right and a molecule of ATP / GTP is obtained. In the reductive citric acid cycle , the reverse reaction takes place in some bacteria (then the SCS are referred to as succinate thiokinases ).

The GDP-forming SCS occur in all living beings (in eukaryotes in the mitochondria ), while the ADP -forming SCS are also found in the cytosol in eukaryotes . In bacteria, the SCS form heterotetramers. In humans, a GDP- and an ADP-forming isozyme dimer ( gene names SUCLG1 / 2 and SUCLG1 / A2 ) are known. Mutations in the human SUCLG1 gene can cause (rare) enzyme deficiencies in the embryo and this infantile lactic acidosis , which is fatal. Defects in SUCLA2 can lead to a very rare mitochondrial metabolic disorder with organ damage. In both cases, methylmalonic acid can be found in the urine.

structure

Bacterial and mammalian SCS are made up of α and β subunits. In E. coli, two αβ heterodimers combine to form a heterotetrameric α2β2 structure. However, mammalian mitochondrial SCS are active as αβ dimers and do not form a heterotetramer.

Individual evidence

  1. ^ JM Berg, JL Tymoczko and L. Stryer: Stryer Biochemistry . 7th ed. Springer, Berlin 2013, ISBN 978-3-8274-2988-9 , pp. 515 .
  2. ↑ UniProt P53597
  3. ↑ Orphanet: Lactic acidosis, infantile congenital
  4. ↑ Orphanet: Mitochondrial DNA Depletion Syndrome
  5. ^ DO Lambeth, KN Tews et al. a .: Expression of two succinyl-CoA synthetases with different nucleotide specificities in mammalian tissues. In: The Journal of biological chemistry Volume 279, Number 35, August 2004, pp. 36621-36624. doi : 10.1074 / jbc.M406884200 . PMID 15234968 .
  6. ↑ Nishimura Js: Succinyl-CoA Synthetase Structure-Function Relationships and Other Considerations. 1986, accessed March 3, 2020 .
  7. ↑ Wolodko Wt, Kay Cm, Bridger Wa: Active Enzyme Sedimentation, Sedimentation Velocity, and Sedimentation Equilibrium Studies of succinyl-CoA Synthetases of Porcine Heart and Escherichia Coli. September 23, 1986, accessed March 3, 2020 .

Web links

Wikibooks: Biochemistry and Pathobiochemistry: Citric Acid Cycle  - Learning and Teaching Materials