Gamma-aminobutyric acid synthesis

Paulsen RE, Odden E, Fonnum F (1988) Importance of glutamine for gamma-aminobutyric acid synthesis in rat neostriatum in vivo. J Neurochem 5 / 1294-1299. 

Gobaille, S., Hechler, V., Andriamampandry, C., Kemmel, V., and Maitre, M. (1999) Gamma-hydroxybutyrate modulates synthesis and extracellular concentration of gamma-aminobutyric acid in discrete rat brain regions in vivo. J. Pharmacol. Exp. Ther 290, 303-309. 

Mechanism of Action An anticonvulsant and antineuralgic agent whose exact mechanism is unknown. May increase the synthesis or accumulation of gamma-aminobutyric acid by binding to as-yet-undefined receptor sites in brain tissue. Therapeutic Effect Reduces seizure activity and neuropathic pain. 

Mechanism of Action Acts as a coenzyme for various metabolic functions, including metabolism of proteins, carbohydrates, and fats. Aids in the breakdown of glycogen and in the synthesis of gamma-aminobutyric acid in the CNS. Therapeutic Effect Prevents pyridoxine deficiency. Increases the excretion of certain drugs, such as iso-niazid, that are pyridoxine antagonists. 

FIGURE 8—16. Gamma-aminobutyric acid (GABA) is produced by synthesis from the precursor amino acid glutamate by the enzyme glutamic acid decarboxylase (Glu-AD). 

Jin H, Wu H, Osterhaus G, Wei J, Davis K, Sha D, Floor E, Hsu CC, Kopke RD, Wu JY (2003) Demonstration of functional coupling between gamma -aminobutyric acid (GABA) synthesis and vesicular GABA transport into synaptic vesicles. Proc Natl Acad Sci USA 100 4293 1298. 

Zafra, F., Castren, E., Thoenen, H. and Lindholm, D. (1991) Interplay between glutamate and gamma-aminobutyric acid transmitter systems in the physiological regulation of brain-derived neurotrophic factor and nerve growth factor synthesis in hippocampal neurons. Proc. Natl. Acad. Sci. USA 88 10037-10041. 

A team at Merck, in 2005, used the Suzuki-Miyaura reaction as a key step in the synthesis of an orally active 2/3-selective GABAA (Gamma-aminobutyric acid receptor) agonist candidate for the treatment of centrtJ nervous system conditions (Scheme 1.43) [143]. The biaryl product was crystallized from water/t-PrOH in 85% and it had a purity of 96.3% (HPLC). 

Some nonstandard amino acids are not found in proteins. Examples include lanthionine, 2-aminoisobutyric acid, dehydroalanine and the neurotransmitter gamma-aminobutyric acid. Nonstandard amino acids often occur as intermediates in the metabolic pathways for standard amino acids — for example ornithine and citrulline occur in the urea cycle, part of amino acid catabolism (see below). A rare exception to the dominance of a-amino acids in biology is the P-amino acid beta alanine (3-aminopropanoic acid), which is used in plants and microorganisms in the synthesis of pantothenic acid (vitamin B5), a component of coenzyme A. 

Kabalka, G. W., Wang, Z., Green, J. F., Goodman, M. M. 1992. Synthesis of isomerically pure nitrogen-13 labeled gamma-aminobutyric acid and putrescine. App. Radiat. Isot. 43 389-391. 

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