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Принадлежит к подразделению: Отдел биокинетики
Руководитель: доктор химических наук, в.н.с., Буник Виктория Ивановна

Cаморегуляция метаболизма за счет катализирующих метаболические реакции ферментов реализуется уже в первичных метаболических сетях и является абсолютно необходимой для поддержания стабильности таких сетей. Механизмы и значение такой саморегуляции рассмотрены в работе [Bunik V., Cellular Networks - Positioning, Performance Analysis, Reliability, 2011]. Отдельные звенья метаболизма отличаются по степени их влияния на поток метаболитов в метаболической сети. В связи с этим решение задач, связанных с направленной регуляцией метаболических потоков в сетях ("metabolic engineering", http://www.ejbiotechnology.info/content/vol1/issue3/full/3/#36), требует определения критических, или ключевых, звеньев метаболизма. К таким звеньям зачастую относятся точки разветвления центрального метаболизма.

Интерес нашей группы фокусируется на точке пересечения метаболизма глюкозы и аминокислот, в которой предшественник глутамата, 2-оксоглутарат, может либо необратимо окислиться с выделением
энергии, либо предоставить углеродный скелет для реакции биосинтеза глутамата. Ключевое положение этой реакции в метаболической сети подчеркивается стремлением биологических систем поддерживать характерное для них соотношение 2-оксоглутарат\глутамат на постоянном уровне. Окисление 2-оксоглутарата катализирует полиферментная система окислительного декарбоксилирования
2-оксоглутарата [Bunik & Strumilo, 2009], возможности регуляции которой на разных уровнях биологической организации, т.е. in vitro (энзимология), in situ (клеточные культуры) и in vivo ( эксперименты на животных), исследуются
нашей группой.



Обновлено 26.08.2015 09:50
Все статьи
  1. Mkrtchyan G., Aleshin V., Parkhomenko Y., Kaehne T., Di Salvo M.L., Parroni A., Contestabile R., Vovk A., Bettendorff L., Bunik V. (2015) Molecular mechanisms of the non-coenzyme action of thiamin in brain: biochemical, structural and pathway analysis. Sci Rep, 5: . >>

  2. Diaz-Munoz M.D., Bell S.E., Fairfax K., Monzon-Casanova E., Cunningham A.F., Gonzalez-Porta M., Andrews S.R., Bunik V.I., Zarnack K., Curk T., Heggermont W.A., Heymans S., Gibson G.E., Kontoyiannis D.L., Ule J., Turner M. (2015) The RNA-binding protein HuR is essential for the B cell antibody response. Nat. Immunol., 16 (4): 415-425. >>

  3. Quinlan C.L., Goncalves R.L.S, Hey-Mogensen M., Yadava N., Bunik V.I., Brand M.D. (2014) The 2-Oxoacid Dehydrogenase Complexes in Mitochondria Can Produce Superoxide/Hydrogen Peroxide at Much Higher Rates Than Complex I. J. Biol. Chem., 289 (12): 8312-8325. >>

  4. Bunik V.I., Tylicki A., Lukashev N.V. (2013) Thiamin diphosphate-dependent enzymes: from enzymology to metabolic regulation, drug design and disease models. FEBS J., 280 (24): 6412-6442. >>

  5. Bunik V.I. (2013) Thiamin-dependent enzymes: new perspectives from the interface between chemistry and biology. FEBS J., 280 (24): 6373-6373. >>

  6. Araujo W.L., Trofimova L., Mkrtchyan G., Steinhauser D., Krall L., Graf A., Fernie A.R., Bunik V.I. (2013) On the role of the mitochondrial 2-oxoglutarate dehydrogenase complex in amino acid metabolism. Amino Acids, 44 (2): 683-700. >>

  7. Graf A., Trofimova L., Loshinskaja A., Mkrtchyan G., Strokina A., Lovat M., Tylicky A., Strumilo S., Bettendorff L., Bunik V.I. (2013) Up-regulation of 2-oxoglutarate dehydrogenase as a stress response. Int. J. Biochem. Cell Biol., 45 (1): 175-189. >>

  8. Parkhomenko Y.M., Kudryavtsev P.A., Pylypchuk S.Y., Chekhivska L.I., Stepanenko S.P., Sergiichuk A.A., Bunik V.I. (2011) Chronic alcoholism in rats induces a compensatory response, preserving brain thiamine diphosphate, but the brain 2-oxo acid dehydrogenases are inactivated despite unchanged coenzyme levels. Journal of Neurochemistry, 117 (6): 1055-1065.

  9. Bunik V.I. (2011) Metabolic Networking through Enzymatic Sensing, Signaling and Response to Homeostatic Fluctuations. Cellular Networks - Positioning, Performance Analysis, Reliability, Agassi Melikov (Ed.), : 377-405. >>

  10. Bunik V.I., Schloss J.V., Pinto J.T., Dudareva N., Cooper A.J. (2011) A survey of oxidative paracatalytic reactions catalyzed by enzymes that generate carbanionic intermediates: implications for ROS production, cancer etiology, and neurodegenerative diseases. Adv Enzymol Relat Areas Mol Biol, 77: 307-60.

  11. Tylicki A., Bunik V.I., Strumiеlo S. (2011) 2-Oxoglutarate dehydrogenase complex and its multipoint control. Postepy Biochem, 57 (3): 304-13.

  12. Trofimova L., Lovat M., Groznaya A., Efimova E., Dunaeva T., Maslova M., Graf A., Bunik V. (2010) Behavioral impact of the regulation of the brain 2-oxoglutarate dehydrogenase complex by synthetic phosphonate analog of 2-oxoglutarate: implications into the role of the complex in neurodegenerative diseases. Int J Alzheimers Dis, 2010: 749061.

  13. Van Der Merwe M.J., Osorio S., Arajo W.L., Balbo I., Nunes-Nesi A., Maximova E., Carrari F., Bunik V.I., Persson S., Fernie A.R. (2010) Tricarboxylic acid cycle activity regulates tomato root growth via effects on secondary cell wall production. Plant Physiol, 153 (2): 611-21.

  14. Graf A., Kabysheva M., Klimuk E., Trofimova L., Dunaeva T., Zundorf G., Kahlert S., Reiser G., Storozhevykh T., Pinelis V., Sokolova N., Bunik V. (2009) Role of 2-oxoglutarate dehydrogenase in brain pathologies involving glutamate neurotoxicity. Journal of Molecular Catalysis B-Enzymatic, 61 (1): 80-87.

  15. Bunik V.I., Fernie A.R. (2009) Metabolic control exerted by the 2-oxoglutarate dehydrogenase reaction: a cross-kingdom comparison of the crossroad between energy production and nitrogen assimilation. Biochemical Journal, 422: 405-421.

  16. Bunik V.I., Strumilo S. (2009) Regulation of Catalysis Within Cellular Network: Metabolic and Signaling Implications of the 2-Oxoglutarate Oxidative Decarboxylation. Current Chemical Biology, 3 (3): 279-290. >>

  17. Kabysheva M.S., Storozhevykh T.P., Pinelis V.G., Bunik V.I. (2009) Synthetic regulators of the 2-oxoglutarate oxidative decarboxylation alleviate the glutamate excitotoxicity in cerebellar granule neurons. Biochemical Pharmacology, 77 (9): 1531-1540.

  18. Zundorf G., Kahlert S., Bunik V.I., Reiser G. (2009) Alpha-Ketoglutarate Dehydrogenase Contributes to Production of Reactive Oxygen Species in Glutamate-Stimulated Hippocampal Neurons in Situ. Neuroscience, 158 (2): 610-616.

  19. Bunik V.I., Kabysheva M.S., Klimuk E.I., Storozhevykh T.P., Pinelis V.G. (2009) Phosphono Analogues of 2-Oxoglutarate Protect Cerebellar Granule Neurons upon Glutamate Excitotoxicity. Natural Compounds and Their Role in Apoptotic Cell Signaling Pathways, 1171: 521-529.

  20. Arajo W.L., Nunes-Nesi A., Trenkamp S., Bunik V.I., Fernie A.R. (2008) Inhibition of 2-oxoglutarate dehydrogenase in potato tuber suggests the enzyme is limiting for respiration and confirms its importance in nitrogen assimilation. Plant Physiol, 148 (4): 1782-96.

  21. Bunik V., Kaehne T., Degtyarev D., Shcherbakova T., Reiser G. (2008) Novel isoenzyme of 2-oxoglutarate dehydrogenase is identified in brain, but not in heart. FEBS Journal, 275 (20): 4990-5006.

  22. Trofimova L.K., Graf A.V., Klimuk E.I., Kabysheva M.S., Sokolova N.A., Bunik V.I. (2008) Phosphonate analogue of ketoglutarate increases activity of ketoglutarate dehydrogenasecomplex in situ and in vivo. European Neuropsychopharmacology, 18: S254-S255.

  23. Bunik V.I., Degtyarev D. (2008) Structure-function relationships in the 2-oxo acid dehydrogenase family: Substrate-specific signatures and functional predictions for the 2-oxoglutarate dehydrogenase-like proteins. Proteins-Structure Function and Bioinformatics, 71 (2): 874-890.

  24. Bunik V.I., Schloss J.V., Pinto J.T., Gibson G.E., Cooper A.J.L. (2007) Enzyme-catalyzed side reactions with molecular oxygen may contribute to cell signaling and neurodegenerative diseases. Neurochemical Research, 32 (4): 871-891.

  25. Bunik V.I., Raddatz G., Wanders R.J.A., Reiser G. (2006) Brain pyruvate and 2-oxoglutarate dehydrogenase complexes are mitochondrial targets of the CoA ester of the Refsum disease marker phytanic acid. FEBS Letters, 580 (14): 3551-3557.

  26. Santos S.S., Gibson G.E., Cooper A.J.L., Denton T.T., Thompson C.M., Bunik V.I., Alves P.M., Sonnewald U. (2006) Inhibitors of the alpha-ketoglutarate dehydrogenase complex alter [1-C-13] glucose and [U-C-13] glutamate metabolism in cerebellar granule neurons. Journal of Neuroscience Research, 83 (3): 450-458.

  27. Bunik V.I., Denton T.T., xu H., Thompson C.M., Cooper A.J.L., Gibson G.E. (2005) Phosphonate analogues of alpha-ketoglutarate inhibit the activity of the alpha-ketoglutarate dehydrogenase complex isolated from brain and in cultured cells. Biochemistry, 44 (31): 10552-10561.

  28. Gibson G.E., Blass J.P., Beal M.F., Bunik V. (2005) The alpha-ketoglutarate-dehydrogenase complex - A mediator between mitochondria and oxidative stress in neurodegeneration. Molecular Neurobiology, 31 (1): 43-63.

  29. Bunik V.I. (2003) 2-oxo acid dehydrogenase complexes in redox regulation - Role of the lipoate residues and thioredoxin. European Journal of Biochemistry, 270 (6): 1036-1042.

  30. Bunik V.I., Sievers C. (2002) Inactivation of the 2-oxo acid dehydrogenase complexes upon generation of intrinsic radical species. European Journal of Biochemistry, 269 (20): 5004-5015.

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