The Glutamate/GABA-Glutamine Cycle: Amino Acid Neurotransmitter Homeostasis (Advances in Neurobiology, 13)

Fundamental biochemical studies of basic brain metabolism focusing on the neuroactive amino acids glutamate and GABA combined with the seminal observation that one of the key enzymes, glutamine synthetase is localized in astroglial cells but not in neurons resulted in the formulation of the term “The Glutamate-Glutamine Cycle.” In this cycle glutamate released from neurons is taken up by surrounding astrocytes, amidated by the action of glutamine synthetase to glutamine which can be transferred back to the neurons. The conversion of glutamate to glutamine is like a stealth technology, hiding the glutamate molecule which would be highly toxic to neurons due to its excitotoxic action. This series of reactions require the concerted and precise interaction of a number of enzymes and plasma membrane transporters, and this volume provides in-depth descriptions of these processes. Obviously such a series of complicated reactions may well be prone to malfunction and therefore neurological diseases are likely to be associated with such malfunction of the enzymes and transporters involved in the cycle. These aspects are also discussed in several chapters of the book. A number of leading experts in neuroscience including intermediary metabolism, enzymology and transporter physiology have contributed to this book which provides comprehensive discussions of these different aspects of the functional importance of the glutamate-glutamine cycle coupling homeostasis of glutamatergic, excitatory neurotransmission to basic aspects of brain energy metabolism. This book will be of particular importance for students as well as professionals interested in these fundamental processes involved in brain function and dysfunction. Front Matter....Pages i-x Introduction to the Glutamate–Glutamine Cycle....Pages 1-7 Glucose, Lactate, β-Hydroxybutyrate, Acetate, GABA, and Succinate as Substrates for Synthesis of Glutamate and GABA in the Glutamine–Glutamate/GABA Cycle....Pages 9-42 Anaplerosis for Glutamate Synthesis in the Neonate and in Adulthood....Pages 43-58 Enzyme Complexes Important for the Glutamate–Glutamine Cycle....Pages 59-98 BCAA Metabolism and NH3 Homeostasis....Pages 99-132 Glutaminases....Pages 133-171 Vesicular Glutamate Uptake....Pages 173-221 The Glutamine Transporters and Their Role in the Glutamate/GABA–Glutamine Cycle....Pages 223-257 Glutamine Metabolism in Gliomas....Pages 259-273 Oligodendrocytes: Development, Physiology and Glucose Metabolism....Pages 275-294 Dysregulation of Glutamate Cycling Mediates Methylmercury-Induced Neurotoxicity....Pages 295-305 Astroglia, Glutamatergic Transmission and Psychiatric Diseases....Pages 307-326 Glutamine Synthetase: Role in Neurological Disorders....Pages 327-350 The Glutamate–Glutamine Cycle in Epilepsy....Pages 351-400 Back Matter....Pages 401-416