Glutamate, synthesis brain

These also presumably lead to a transient quinonoid-carbanionic intermediate. Addition of a proton at the original site of decarboxylation followed by breakup of the Schiff base completes the sequence. Decarboxylation of amino acids is nearly irreversible and frequently appears as a final step in synthesis of amino compounds. For example, in the brain glutamic acid is decarboxy-lated to y-aminobutyric acid (Gaba),193 196b while 3,4-dihydroxyphenylalanine (dopa) and 5-hydroxy-... 

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. 

Aspartate, like glutamate, is an excitatory neurotransmitter, but it functions in far fewer pathways. It is synthesized from the TCA cycle intermediate oxaloacetate via transamination reactions. Like glutamate synthesis, aspartate synthesis uses oxaloacetate that must be replaced through anaplerotic reactions. Aspartate cannot pass through the blood-brain barrier. 

In the case of hyperphenylalaninaemia, which occurs ia phenylketonuria because of a congenital absence of phenylalanine hydroxylase, the observed phenylalanine inhibition of proteia synthesis may result from competition between T.-phenylalanine and L-methionine for methionyl-/RNA. Patients sufferiag from maple symp urine disease, an inborn lack of branched chain oxo acid decarboxylase, are mentally retarded unless the condition is treated early enough. It is possible that the high level of branched-chain amino acids inhibits uptake of L-tryptophan and L-tyrosiae iato the brain. Brain iajury of mice within ten days after thek bkth was reported as a result of hypodermic kijections of monosodium glutamate (MSG) (0.5—4 g/kg). However, the FDA concluded that MSG is a safe kigredient, because mice are bom with underdeveloped brains regardless of MSG kijections (106). 

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). 

Monaghan, D. T., McMills, M. C., Chamberlin, A. R., Cotman, C. W. Synthesis of [3H]2-amino-4-phosphonobutyric acid and characterization of its binding to rat brain membranes a selective ligand for the chloride/calcium-dependent class of L-glutamate binding sites, Brain Res. 1983, 278, 137-144. 

---