Glutamate dehydrogenase is essential to sustain neuronal oxidative energy metabolism during stimulation

作者: Michaela C Hohnholt , Vibe H Andersen , Jens V Andersen , Sofie K Christensen , Melis Karaca

DOI: 10.1177/0271678X17714680

关键词:

摘要: The enzyme glutamate dehydrogenase (GDH; Glud1) catalyzes the (reversible) oxidative deamination of to α-ketoglutarate accompanied by a reduction NAD+ NADH. GDH connects amino acid, carbohydrate, neurotransmitter and energy metabolism. Glutamine is precursor used neurons sustain pool glutamate, but glutamine also vividly oxidized for support This study investigates role in neuronal metabolism employing Cns- Glud1-/- mouse, lacking brain (GDH KO) metabolic mapping using 13C-labelled glucose. We observed severely reduced during glucose deprivation synaptosomes cultured not expressing GDH. In contrast, presence glucose, was affected lack expression. Respiration fuelled significantly lower mitochondria from KO mice were able increase their respiration upon an elevated demand. respiratory capacity underscore importance particularly demand, it may reflect large allosteric activation ADP.

参考文章(42)
M Yudkoff, D Nelson, Y Daikhin, M Erecińska, Tricarboxylic acid cycle in rat brain synaptosomes. Fluxes and interactions with aspartate aminotransferase and malate/aspartate shuttle. Journal of Biological Chemistry. ,vol. 269, pp. 27414- 27420 ,(1994) , 10.1016/S0021-9258(18)47001-9
Cleanthe Spanaki, Dimitra Kotzamani, Kleopas Kleopa, Andreas Plaitakis, Evolution of GLUD2 Glutamate Dehydrogenase Allows Expression in Human Cortical Neurons Molecular Neurobiology. ,vol. 53, pp. 5140- 5148 ,(2016) , 10.1007/S12035-015-9429-2
A. Lewis Farr, Oliver H. Lowry, Rose J. Randall, Nira J. Rosebrough, Protein Measurement with the Folin Phenol Reagent Journal of Biological Chemistry. ,vol. 193, pp. 265- 275 ,(1951)
Jakob D. Nissen, Kamilla Pajęcka, Malin H. Stridh, Dorte M. Skytt, Helle S. Waagepetersen, Dysfunctional TCA-Cycle Metabolism in Glutamate Dehydrogenase Deficient Astrocytes Glia. ,vol. 63, pp. 2313- 2326 ,(2015) , 10.1002/GLIA.22895
Keetae Kim, Seok-Geun Lee, Timothy P. Kegelman, Zhao-Zhong Su, Swadesh K. Das, Rupesh Dash, Santanu Dasgupta, Paola M. Barral, Michael Hedvat, Paul Diaz, John C. Reed, John L. Stebbins, Maurizio Pellecchia, Devanand Sarkar, Paul B. Fisher, Role of Excitatory Amino Acid Transporter‐2 (EAAT2) and glutamate in neurodegeneration: Opportunities for developing novel therapeutics Journal of Cellular Physiology. ,vol. 226, pp. 2484- 2493 ,(2011) , 10.1002/JCP.22609
F. Rothe, M. Brosz, J. Storm-Mathisen, Quantitative ultrastructural localization of glutamate dehydrogenase in the rat cerebellar cortex Neuroscience. ,vol. 64, pp. 1133- 1146 ,(1995) , 10.1016/0306-4522(94)E0200-N
Patrik Verstreken, Cindy V. Ly, Koen J.T. Venken, Tong-Wey Koh, Yi Zhou, Hugo J. Bellen, Synaptic Mitochondria Are Critical for Mobilization of Reserve Pool Vesicles at Drosophila Neuromuscular Junctions Neuron. ,vol. 47, pp. 365- 378 ,(2005) , 10.1016/J.NEURON.2005.06.018
Ti-Zhi Su, Gregory W Campbell, Dale L Oxender, Glutamine transport in cerebellar granule cells in culture. Brain Research. ,vol. 757, pp. 69- 78 ,(1997) , 10.1016/S0006-8993(97)00139-X