Metabolon

In biochemistry, a metabolon is a temporary structural-functional complex formed between sequential enzymes of a metabolic pathway, held together by non-covalent interactions, and structural elements of the cell such as integral membrane proteins and proteins of the cytoskeleton.

The formation of metabolons allows passing (channelling) the intermediary metabolic product from an enzyme directly as substrate into the active site of the consecutive enzyme of the metabolic pathway. The citric acid cycle is an example of a metabolon which facilitates substrate channeling.[1] During the functioning of metabolons, the amount of water needed to hydrate the enzymes is reduced and enzyme activity is increased.

History

The concept of structural-metabolic cellular complexes was first conceived in 1970 by A. M. Kuzin of the USSR Academy of Sciences,[2] and adopted in 1972 by P. A. Srere of the University of Texas for the enzymes of the citric acid cycle.[3] This hypothesis was well accepted in the former USSR and further developed for the complex of glycolytic enzymes (Embden-Meyerhof-Parnas pathway) by B.I. Kurganov and A.E. Lyubarev.[4][5][6][7] In the mid-1970s, the group of F.M. Clarke at the University of Queensland, Australia also worked on the concept.[8][9] The name “metabolon” was first proposed in 1985 by P. Srere[10] during a lecture in Debrecen, Hungary.[11]

Metabolic pathways in which occurs formation of metabolons
Metabolic pathway Events supporting metabolon's formation
DNA biosynthesisA, B, C, E, F
RNA biosynthesis A, B, C, E, F
Protein biosynthesisA, B, C, D, E
Glycogen biosynthesisC, E
Pyrimidine biosynthesisA, C, D, F
Purine biosynthesisA, E
Lipid biosynthesisA, B, C, H
Steroid biosynthesisA, C, E
Metabolism of amino acidsA, B, D, H
GlycolysisA, B, C, D, I
Citric acid cycleB, C, D, E, G
Fatty acids oxidationA, B, C, D
Electron transport chainC, I
Antibiotic biosynthesisA, E
Urea cycleB, D
cAMP degradationA, D, E
A - Channeling, B - Specific protein-protein interactions, C - Specific protein - membrane interactions, D - Kinetic effects, E - Multienzyme complexes identified, F - Genetic proofs, G - Operative modeled systems, H - Identified multifunctional proteins, I - Physico-chemical proofs.[12]

See also

References

  1. ↑ Wu, Fei; Minteer, Shelley (2 February 2015). "Krebs Cycle Metabolon: Structural Evidence of Substrate Channeling Revealed by Cross-Linking and Mass Spectrometry". Angewandte Chemie International Edition 54 (6): 1851–1854. doi:10.1002/anie.201409336.
  2. ↑ Kuzin A. M. Structural – metabolic hypothesis in radiobiology. Moscow: Nauka Ed., 1970.- 50 p.
  3. ↑ Srere P. A. Is there an organization of Krebs cycle enzymes in the mitochondrial matrix? In: Energy Metabolism and the Regulation of Metabolic Processes in Mitochondria, R. W. Hanson and W.A. Mehlman (Eds.). New York: Academic Press. 1972. p.79-91.
  4. ↑ Lyubarev, A. E.; Kurganov, B. I. (1989). "Supramolecular organization of tricarboxylic acid cycle enzymes". Biosystems 22 (2): 91. doi:10.1016/0303-2647(89)90038-5.
  5. ↑ Lyubarev A. E., Kurganov B. I. Supramolecular organisation of Tricarboxylic Acids Cycle’s enzymes. Proceedings of the All-Union Symposium “Molecular mechanisms and regulation of energy metabolism”. Puschino, Russia, 1986. p. 13. (in Russian) .
  6. ↑ Kurganov B. I, Lyubarev A. E. Hypothetical structure of the complex of glycolytic enzymes (glycolytic metabolon), formed on the membrane of erythrocytes. Molek. Biologia. 1988. V.22, No.6, p. 1605-1613. (in Russian)
  7. ↑ Kurganov B.I., Lyubarev A.E. Enzymes and multienzyme complexes as controllable systems. In: Soviet Scientific Reviews. Section D. Physicochemical Biology Reviews. V. 8 (ed. V.P. Skulachev). Glasgow, Harwood Acad. Publ., 1988, p. 111-147
  8. ↑ Clarke, F. M.; Masters, C. J. (1975). "On the association of glycolytic enzymes with structural proteins of skeletal muscle". Biochimica et Biophysica Acta (BBA) - General Subjects 381: 37. doi:10.1016/0304-4165(75)90187-7.
  9. ↑ Clarke, F. M.; Stephan, P.; Huxham, G.; Hamilton, D.; Morton, D. J. (1984). "Metabolic dependence of glycolytic enzyme binding in rat and sheep heart". European Journal of Biochemistry 138 (3): 643. doi:10.1111/j.1432-1033.1984.tb07963.x.
  10. ↑ Srere, P. A. (1985). "The metabolon". Trends in Biochemical Sciences 10 (3): 109. doi:10.1016/0968-0004(85)90266-X.
  11. ↑ Robinson, J. B., Jr. & Srere, P. A. (1986) Interactions of sequential metabolic enzymes of the mitochondria: a role in metabolic regulation, pp. 159–171 in Dynamics of Biochemical Systems (ed. Damjanovich, S., Keleti, T. & Trón, L.), Akadémiai Kiadó, Budapest, Hungary
  12. ↑ Veliky M.M., Starikovich L. S., Klimishin N. I., Chayka Ya. P. Molecular mechanisms in the integration of metabolism. Lviv National University Ed., Lviv, Ukraine. 2007. 229 P.(in ukrainian)[ISBN 978-966-613-538-7]
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