tailieunhanh - Báo cáo khoa học: Novel isoenzyme of 2-oxoglutarate dehydrogenase is identified in brain, but not in heart

2-Oxoglutarate dehydrogenase (OGDH) is the first and rate-limiting com-ponent of the multienzyme OGDH complex (OGDHC) whose malfunction is associated with neurodegeneration. The essential role of this complex in the degradation of glucose and glutamate, which have specific significance in brain, raises questions about the existence of brain-specific OGDHC iso-enzyme(s). | ễFEBS Journal Novel isoenzyme of 2-oxoglutarate dehydrogenase is identified in brain but not in heart Victoria Bunik1 2 Thilo Kaehne3 Dmitry Degtyarev1 Tatiana Shcherbakova2 and Georg Reiser4 1 Bioengineering and Bioinformatics Department Lomonosov Moscow State University Russia 2 Belozersky Institute of Physico-ChemicalBiology Lomonosov Moscow State University Russia 3 Institute of ExperimentalInternalMedicine Otto-von-Guericke University Magdeburg Germany 4 Institute of Neurobiochemistry MedicalFaculty Otto-von-Guericke University Magdeburg Germany Keywords 2-oxoglutarate dehydrogenase isoenzyme mitochondrialmembrane multienzyme complex thiamine tricarboxylic acid cycle Correspondence V. Bunik Belozersky Institute of Physico-ChemicalBiology Lomonosov Moscow State University Moscow 119992 Russia Fax 7 495 939 31 81 Tel 7 495 939 44 84 E-mail bunik@ G. Reiser Institut fijr Neurobiochemie Medizinische Fakultat Otto-von-Guericke-Universitat Magdeburg Leipziger StraBe 44 39120 Magdeburg Germany Fax 49 391 67 13097 Tel 49 391 67 13088 E-mail Received 17 April2008 revised 5 July 2008 accepted 8 August 2008 doi 2-Oxoglutarate dehydrogenase OGDH is the first and rate-limiting component of the multienzyme OGDH complex OGDHC whose malfunction is associated with neurodegeneration. The essential role of this complex in the degradation of glucose and glutamate which have specific significance in brain raises questions about the existence of brain-specific OGDHC iso-enzyme s . We purified OGDHC from extracts of brain or heart mitochondria using the same procedure of poly ethylene glycol fractionation followed by size-exclusion chromatography. Chromatographic behavior and the insufficiency of mitochondrial disruption to solubilize OGDHC revealed functionally significant binding of the complex to membrane. Components of OGDHC from brain and heart were identified using nano-high performance liquid .