Glutamate, synthesis astrocytes

Fig. 5. Glutamine cycle formed between excitatory nerve endings and astrocytes and de novo synthesis of glutamate in astrocytes (cf. Chapter I). Modified from Kaneko et al. (1988a).

Glutamine synthetase, a brain Mn enzyme, is located mainly in astrocytes, and its synthesis may be modulated by nitric oxide (496). Inhibition of this enzyme could be relevant to aging diseases (497). There is evidence that human NT2-N neurons die via ionotropic glutamate receptor-mediated mechanisms when exposed to hypoxia in the presence of glutamate (498). 

This transfer of reducing equivalents is essential for maintaining the favorable NAD+/NADH ratio required for the oxidative metabolism of glucose and synthesis of glutamate in brain (McKenna et al., 2006). The malate-aspartate shuttle is considered the most important shuttle in brain. It is particularly important in neurons. It has low activity in astrocytes. This shuttle system is fully reversible and linked to amino acid metabolism with the energy charge and citric acid cycle of neuronal cells. 

Gamberino WC, Berkich DA, Lynch CJ, Xu B, LaNoue KF (1997) Role of pyruvate carboxylase in facilitation of synthesis of glutamate and glutamine in cultured astrocytes. J Neurochem 69 2312-2325. 

Fig. 10. Synthesis and metabolism of glutamate and GABA in excitatory and inhibitory neurons in combination with astrocytic metabolism. The figure is modified from Kaneko and Mizuno (1994).

Fig. 13.2 Schematic of the Neuroprotective Gamma Glutamyl Cycle One of the neuroprotective roles of cortical astrocytes is maintenance of neuron glutathione (GSH) homeostasis. Astrocytes contain a highly effective GSH synthesis capacity and readily export the intact tripeptide into the extracellular milieu. The extrusion process is likely mediated by a multidrug resistance associated protein (Mrp). Once GSH is in the external compartment, it is hydrolyzed gamma glutamyl transpeptidase (7GT) to the dipeptide CysGly and glutamate. The dipeptide hydrolysis product is cleaved further by aminopeptidase N (APN) on the surface of the neuron to Cys and Gly. Cysteine is then transported into the neuron where it is a key determinant of neuron GSH synthesis (See also Color Insert)...

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