GABA from glutamic acid

Amino acid decarboxylations are involved in the synthesis of several metabolically important amines, e.g., 5-hydroxytryptamine (serotonin) from tryptophan, histamine from histidine, and y-aminohutyric acid (GABA) from glutamate. 

Levi G, Gallo V (1981) Glutamate as a putative transmitter in the cerebellum stimulation by GABA of glutamic acid release from specific pools. J Neurochem 37 22-31. 

Gamma-aminobutyric acid (GABA) which derives from glutamic acid via decarboxylation is the most important inhibitory neurotransmitter of inhibitory neurons of the CNS, most of them intemeurons. Approximately 30% of all central synapses are GABAergic. Pentameric GABAa receptors (similar structure as nAChR Fig. 4) modulate a CF channel,... 

GABA is an inhibitory amino acid neurotransmitter of brain interneurons and other cerebral neurons. The enzyme glutamic acid decarboxylase catalyzes the synthesis of GABA from glutamate. GABA is stored in presynaptic vesicles and binds to either GABA-A or GABA-B receptors upon release. 

Alkaloids derived from glutamic acid, other than y-aminobutyric acid (GABA), include kainic acid isolated from Digenea simplex, domoic acid isolated from Chondria armata, acromelic acids isolated from Clitocybe acromelalga, ibotenic acid isolated from Amanita strobiliformis Amanita pantherina), and tricholomic acid isolated from Tricholoma musucaria, and are described in this chapter. 

FIGURE 17.5 Synthesis of nylon 4 from glutamic acid via GABA and 2-pyrrolidone. 

Certain amino acids and their derivatives, although not found in proteins, nonetheless are biochemically important. A few of the more notable examples are shown in Figure 4.5. y-Aminobutyric acid, or GABA, is produced by the decarboxylation of glutamic acid and is a potent neurotransmitter. Histamine, which is synthesized by decarboxylation of histidine, and serotonin, which is derived from tryptophan, similarly function as neurotransmitters and regulators. /3-Alanine is found in nature in the peptides carnosine and anserine and is a component of pantothenic acid (a vitamin), which is a part of coenzyme A. Epinephrine (also known as adrenaline), derived from tyrosine, is an important hormone. Penicillamine is a constituent of the penicillin antibiotics. Ornithine, betaine, homocysteine, and homoserine are important metabolic intermediates. Citrulline is the immediate precursor of arginine. 

If a substance is to be a NT it should be possible to demonstrate appropriate enzymes for its synthesis from a precursor at its site of action, although peptides are transported to their sites of location and action after synthesis in the axon or distal neuronal cell body. The specificity of any enzyme system must also be established, especially if they are to be modified to manipulate the levels of a particular NT, or used as markers for it. Thus choline acetyltransferase (ChAT) may be taken as indicative of ACh and glutamic acid decarboxylase (GAD) of GABA but some of the synthesising enzymes for the monoamines lack such specificity. 

Fig. 5.12 (a) Synaptic types along dendritic spines of M/T and GC units uni-, and bi-directional junctions, (b) Transmitter systems at a reciprocal synapse, Mitral-Granule cell junction. [Glu, glutamate (R, receptor) GABA, y-aminobutyric acid (R, receptor) E, intracellular effector and aAR, alpha-adrenergic receptor.]. (From Hayashi et al., 1993.)... 

---