3.2 Glial–Neuronal Shuttle Systems

摘要: The glutamine–glutamate cycle between astrocytes and neurons is an essential part of neuronal function activity. However, this not stoichiometric modulated by different regulatory mechanisms. By means, in particular, the are flexible their intracellular regulation metabolism ability to support form energy substrates precursors for neurotransmitter glutamate. Among conventional biochemical molecular studies, ex vivo vitro C‐NMR spectroscopy has been used monitor neural function, tissue metabolism, neuronal–glial metabolic interactions. Special emphasis given specialization its enzymatic regulation. For purpose primary cell cultures useful tools study relationships as extracellular fluid can be investigated manipulated various stimuli. In cultured astrocytes, glucose utilized predominantly anaerobically. Glycolysis interrelated astrocytic tricarboxylic acid (TCA) via bidirectional signals exchange processes neurons. Besides oxidation, neuronally released glutamate metabolized through glial TCA cycle, while astrocyte‐derived glutamine substrate precursor. flexibility glutamate‐ depends on ammonia‐ homeostasis, pyruvate recycling pathway modulates cycle. studies have further extended concept “nonstoichiometric” glutamate–glutamine alanine/lactate well leucine/a‐ketoisocaproate (a‐KIC) shuttles astrocytes. These contribute nitrogen transfer from neurons, thereby promoting intercellular glutamine– cycling. provision regulated intracytosolic compartmentation essence, compartmentalized buffers brain against impairments excitotoxicity response knowledge about these mechanisms important understanding physiological pathophysiological general function. List Abbreviations: ALAT, alanine aminotransferase; BBB, blood–brain barrier; BCAA, branched‐chain amino acid; cME, cytoplasmic malic enzyme; GABA, g‐aminobutyric GDH, dehydrogenase; GS, synthetase; HE, hepatic encephalopathy; a‐KIC, a‐ketoisocaproate; LDH, lactate ME, mME, mitochondrial MSO, methionine–sulfoximine; PAG, phosphate‐activated glutaminase; PC, carboxylase; PDH, 3‐NPA, 3‐nitropropionic PEPCK, phosphoenolpyruvate carboxykinase; PK, kinase; PEP, phosphoenolpyruvate; TBOA, D,L‐threo‐b‐benzyloxyaspartate; TCA,