Metabolon

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

The concept of structural-metabolic cellular complexes was first conceived in 1970 by A. M. Kuzin of the USSR Academy of Sciences^[1], and adopted in 1972 by P. A. Srere of the University of Texas for the enzymes of the Tricarboxilic Acids (Szent Györgyi-Krebs) Cycle^[2]. 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^[3][4][5]. In the middle 70’s the group of F.M. Clarke at the University of Queensland, Australia also worked on the concept ^[6][7]. The name “METABOLON” was first proposed in 1985 by P. Srere^[8] during a lecture in Debrecen, Hungary^[9].

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 Kreb's Cycle (Tricarboxylic Acid Cycle, Citric Acid Cycle) is an example of a metabolon which facilitates substrate channeling. During the functioning of metabolons the amount of water needed to hydrate the enzymes is reduced and the enzyme activity is increased^{[citation needed]}.

Metabolic pathways in which occuurs formation of metabolons 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 Tricarboxilic acids cycle B,C,D,E,G Fatty acids oxidation A,B,C,D Electron transport C,I Antiobiotic 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.[10] See also Enzyme kinetics Enzyme assay Enzyme catalysis References ^ 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 mitochondiral 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. Suprampolecular organisation of Tricarboxilic Acids Cycle’s enzymes. Proccedings 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 FM, Masters CJ. On the association of glycolytic enzymes with structural proteins of skeletal muscle Biochim Biophys Acta. 1975;381(1):37-46. ^ Clarke FM, Stephan P, Huxham G, Hamilton D, Morton DJ. Metabolic dependence of glycolytic enzyme binding in rat and sheep heart.Eur J Biochem. 1984;138(3):643-9 ^ Srere PA (1985) The metabolon. Trends Biochem Sci 10:109–110.[4] ^ 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 ^ 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]