Glutamate, synthesis

This has obvious advantages over the process seen for glutamate synthesis via the reductive amination of 2-oxoglutarate, in that it no longer requires the intervention of free ammonia. We thus have the situation that some organisms are able to carry out the fixation of ammonia via reductive amination, whereas others manipulate via transamination the amino acid structures obtained from protein in the diet. 

Buchanan, Bachofen, and Arnon (29) found that extracts from Chromatium catalyzed a synthesis of pyruvate from acetyl-CoA, CO2, and reduced ferredoxin. Pyruvate did not accumulate in the absence of a trap, but was converted mainly to the amino acids, alanine, aspartate, and glutamate. Synthesis of these amino acids from acetate and CO2, by way of pyruvate, was in agreement with the earlier labeling data of Tomlinson (102) with anaerobic bacteria and of Cutinelli et al. (34) with another photosynthetic bacterium, Rhodospirillum rubrum. 

Either or both of these compounds in high concentration will favor glutamate synthesis in the reaction catalyzed by glutamate dehydrogenase. This shift of the chemical reaction to the right will result in assimilation of ammonia. 

Glutamate is derived by transamination of a-keto-glutarate produced in the TCA cycle from citrate via oxaloacetate and acetyl-CoA (Chapter 13). All of the amino acids can produce acetyl-CoA. All except leucine and lysine (which are oxidized solely to acetyl-CoA) can be used in net synthesis of a-ketoglutarate to enhance glutamate synthesis. Ammonia is generated in glutamate dehydrogenase and AMP deaminase reactions (Chapter 21). 

Fonnum F, Hassel B (1995) Glutamate synthesis, metabolism, and uptake. In Stone TW (Ed). CNS Neurotransmitters and Neuromodulators Glutamate. New York CRC Press, pp 19-34. 

In the following sections, I will first review the distribution of glutaminase in the brain, then describe glutamate synthesis and metabolism in glial cells, and finally discuss the role of glutamate and AAT in GABAergic neurons. 

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