Neuronal-astrocytic and cytosolic-mitochondrial metabolite trafficking during brain activation, hyperammonemia and energy deprivation

• Published in: Neurochemistry international 2000-08, Vol.37 (2), p.83-102
• Main Authors: Hertz, Leif, Yu, Albert C.H., Kala, Geeta, Schousboe, Arne
• Format: Article
• Language: English
• Subjects: Ammonia - blood; Ammonia toxicity; Animals; Astrocytes; Astrocytes - metabolism; Astrocytes - physiology; Biochemistry and metabolism; Biological and medical sciences; Brain - physiology; Central nervous system; Cerebral ischemia; Cytosol - metabolism; Energy Metabolism - physiology; Fundamental and applied biological sciences. Psychology; Glucose - deficiency; Glucose - metabolism; Glutamate metabolism; Glutamate-glutamine cycle; Glutamic Acid - metabolism; Humans; hyperammonemia; Neurons; Neurons - metabolism; Neurons - physiology; Pyruvate carboxylation; Vertebrates: nervous system and sense organs
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/S0197-0186(00)00012-7

A novel concept is described, according to which both neurons and astrocytes are capable of metabolizing glucose all the way to CO 2 and water, but in addition interact metabolically in a process generating glutamate from glucose, and subsequently, metabolizing excess glutamate to CO 2 and water Hertz, L., Dringen, R., Schousboe, A., Robinson, S.R., 1999. Astrocytes: Glutamate producers for neurons (Journal of Neuroscience Research 57, 417–428). The proposed metabolic degradation of glucose via glutamate serves the purpose of adjusting transmitter pools of glutamate to the demands for glutamatergic transmission, and it must account for a major fraction of glucose utilization. Evidence in favor of this concept is presented and a multitude of in vivo data are interpreted in the context of metabolic trafficking between neurons and astrocytes. In addition, intracellular trafficking occurs between cytosol and mitochondria during synthesis of transmitter glutamate, partly explaining a robust quantitative correlation betwen glutamine synthesis, as a measure of release of transmitter glutamate, and glucose utilization, reported by several authors. Both intracellular and intercellular metabolic trafficking may be affected during pathological conditions, as evidenced by effects of hyperammonemia (mimicking hepatic encephalopathy) and energy deprivation (mimicking stroke). It is suggested that neuronal-astrocytic interactions may also be impaired during degenerative dementing diseases.