Inbiochemistry,ametabolonis a temporary structural-functional complex formed between sequentialenzymesof ametabolic pathway,held together both bynon-covalent interactionsand by structural elements of the cell, such asintegral membrane proteinsand proteins of thecytoskeleton.
The formation of metabolons allows the intermediate product from one enzyme to be passed(channelling)directly into the active site of the next consecutive enzyme of the metabolic pathway. Thecitric acid cycleis an example of a metabolon that facilitates substrate channeling.[1][2]Another example is the dhurrin synthesis pathway in sorghum, in which the enzymes assemble as a metabolon in lipid membranes.[3]During the functioning of metabolons, the amount of water needed to hydrate the enzymes is reduced and enzyme activity is increased[citation needed].
History
editThe concept of structural-metabolic cellular complexes was first conceived in 1970 by A. M. Kuzin of the USSR Academy of Sciences,[4]and adopted in 1972 by Paul A. Srere of theUniversity of Texasfor the enzymes of thecitric acid cycle.[5]This hypothesis was well accepted in the former USSR and further developed for the complex ofglycolyticenzymes (Embden-Meyerhof-Parnas pathway) by B.I. Kurganov and A.E. Lyubarev.[6][7][8][9]In the mid-1970s, the group of F.M. Clarke at theUniversity of Queensland,Australia also worked on the concept.[10][11]The name "metabolon" was first proposed in 1985 by Paul Srere[12]during a lecture in Debrecen, Hungary.[13]
The case of Fatty Acid Synthesis
editInChaetomium thermophilum,a complex of a metabolon exists between fatty acid synthase and a MDa carboxylase,[14]and was observed using chemical cross-linking coupled tomass spectrometryand visualized bycryo-electron microscopy.The Fatty acid synthesis metabolon inC. thermophilumis highly flexible, and although a high-resolution structure ofFatty acid synthasewas possible, the metabolon was highly flexible, hindering high-resolution structure determination.[citation needed]
Examples
edit| Metabolic pathways in which formation of metabolons occurs | |||||
|---|---|---|---|---|---|
| Metabolic pathway | Events supporting metabolon's formation | ||||
| DNA biosynthesis | A, B, C, E, F | ||||
| RNA biosynthesis | A, B, C, E, F | ||||
| Protein biosynthesis | A, B, C, D, E | ||||
| Glycogen biosynthesis | C, E | ||||
| Pyrimidine biosynthesis | A, C, D, F | ||||
| Purine biosynthesis | A, E | ||||
| Lipid biosynthesis | A, B, C, H | ||||
| Steroid biosynthesis | A, C, E | ||||
| Metabolism of amino acids | A, B, D, H | ||||
| Glycolysis | A, B, C, D, I | ||||
| Citric acid cycle | B, C, D, E, G | ||||
| Fatty acids oxidation | A, B, C, D | ||||
| Electron transport chain | C, I | ||||
| Antibiotic biosynthesis | A, E | ||||
| Urea cycle | B, D | ||||
| cAMP degradation | A, 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.[15] | |||||
See also
editReferences
edit- ^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.PMID25537779.
- ^Zhang, Youjun; Beard, Katherine F. M.; Swart, Corné; Bergmann, Susan; Krahnert, Ina; Nikoloski, Zoran; Graf, Alexander; Ratcliffe, R. George; Sweetlove, Lee J.; Fernie, Alisdair R.; Obata, Toshihiro (16 May 2017)."Protein-protein interactions and metabolite channelling in the plant tricarboxylic acid cycle".Nature Communications.8:15212.doi:10.1038/ncomms15212.PMC5440813.PMID28508886.
- ^Laursen, Tomas; Borch, Jonas; Knudsen, Camilla; Bavishi, Krutika; Torta, Federico; Martens, Helle Juel; Silvestro, Daniele; Hatzakis, Nikos S.; Wenk, Markus R. (2016-11-18)."Characterization of a dynamic metabolon producing the defense compound dhurrin in sorghum"(PDF).Science.354(6314): 890–893.doi:10.1126/science.aag2347.ISSN0036-8075.PMID27856908.S2CID19187608.
- ^Kuzin A. M. Structural – metabolic hypothesis in radiobiology. Moscow: Nauka Ed., 1970.- 50 p.
- ^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.
- ^Lyubarev, A. E.; Kurganov, B. I. (1989). "Supramolecular organization of tricarboxylic acid cycle enzymes".Biosystems.22(2): 91–102.doi:10.1016/0303-2647(89)90038-5.PMID2720141.
- ^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)[1].
- ^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)[2]
- ^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[3]
- ^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(1): 37–46.doi:10.1016/0304-4165(75)90187-7.PMID1111588.
- ^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): 643–9.doi:10.1111/j.1432-1033.1984.tb07963.x.PMID6692839.
- ^Srere, P. A. (1985). "The metabolon".Trends in Biochemical Sciences.10(3): 109–110.doi:10.1016/0968-0004(85)90266-X.
- ^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
- ^Kastritis, Panagiotis L.; O'Reilly, Francis J.; Bock, Thomas; Li, Yuanyue; Rogon, Matt Z.; Buczak, Katarzyna; Romanov, Natalie; Betts, Matthew J.; Bui, Khanh Huy (2017-07-01)."Capturing protein communities by structural proteomics in a thermophilic eukaryote".Molecular Systems Biology.13(7): 936.doi:10.15252/msb.20167412.ISSN1744-4292.PMC5527848.PMID28743795.
- ^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)ISBN978-966-613-538-7