Y-aminobutyric acid 2? -amino acids

Evidence is lacking for the presence of the amino acids, y-aminobutyric acid (GABA), glutamic acid, aspartic acid and glycine, which are believed to play a role as transmitter substances in vertebrates and other invertebrates. 

Some of the less common d enantiomers of amino acids are also found in nature. For example, D-glutamic acid is found in the cell walls of many bacteria, and D-serine is found in earthworms. Some naturally occurring amino acids are not a-amino acids y-Aminobutyric acid (GABA) is one of the neurotransmitters in the brain, and jS-alanine is a constituent of the vitamin pantothenic acid. 

ACh interacts with the nicotinic ACh receptor to initiate an end-plate potential (EPP) in muscle or an excitatory postsynaptic potential (EPSP) in peripheral ganglia (Chapter 6). The nicotinic receptor of vertebrate skeletal muscle is a pentamer composed of 4 distinct subunits a, /3, y, and S) in the stoichiometric ratio of 2 1 1 1, respectively. In mature, innervated muscle end plates, the y subunit is replaced by the closely related e subunit. The nicotinic receptor is prototypical of other pen-tameric ligand-gated ion channels, which include the receptors for the inhibitory amino acids (y-aminobutyric acid [GABA] and glycine) and S-HT serotonin receptors (Figure 9-1). 

The amino acid y-aminobutyric acid functions in the body as a neurotransmitter. It is also found in silage as a fermentation product of glutamic acid (see p. 502). 

Amino acid y-Aminobutyric acid (rice) Hypertension... 

Aminobutanoic acid known as y-aminobutyric acid (GABA), it is a y-amino acid and is involved in the transmission of nerve impulses... 

One of the amino acids in Table 27.1 is the biological precursor to y-aminobutyric acid (4-aminobutanoic acid), which it forms by a decarboxylation reaction. Which amino acid is this ... 

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. 

GABA (y-aminobutyric acid) is an amino acid with mostly inhibitory functions in the mammalian central nervous system. Structures involved in releasing or binding GABA as a neurotransmitter constitute the GABAergic system. The GABAergic system is involved... 

Of the twenty amino acids that are normally found in proteins, only two contain sulfur, cysteine and methionine. Cysteine has long been recognized as being easily oxidized and this oxidation is associated with the loss of biological activity of many proteins. In recent years, it has been shown that methionine also shares these characteristics. Methionine was first isolated by Mueller19 and was one of the last amino acids discovered. Its structure was later proven to be y-methylthio-a-aminobutyric acid by Barger and Coyne20 who named the amino acid methionine as a contraction for its chemical name. 

Nofe. AMPA = amino-3-hydroxy-5--methyl-4-isoxazole propionate GABA=y-aminobutyric acid. 

Important products derived from amino acids include heme, purines, pyrimidines, hormones, neurotransmitters, and biologically active peptides. In addition, many proteins contain amino acids that have been modified for a specific function such as binding calcium or as intermediates that serve to stabilize proteins—generally structural proteins—by subsequent covalent cross-hnk-ing. The amino acid residues in those proteins serve as precursors for these modified residues. Small peptides or peptide-like molecules not synthesized on ribosomes fulfill specific functions in cells. Histamine plays a central role in many allergic reactions. Neurotransmitters derived from amino acids include y-aminobutyrate, 5-hydroxytryptamine (serotonin), dopamine, norepinephrine, and epinephrine. Many drugs used to treat neurologic and psychiatric conditions affect the metabolism of these neurotransmitters. 

Figure 31-7. Metabolism of y-aminobutyrate. (a-KA, a-keto acids a-AA, a-amino acids PLP, pyri-doxal phosphate.)...

GABA receptors. Receptors for y-aminobutyric acid. GABA is an amino acid that acts as an inhibitory neurotransmitter in the CNS. 

False neurotransmitters resulting from increased levels of aromatic amino acids, high levels of y-aminobutyric acid, and endogenous benzodiazepines have also been implicated in HE. These substances bind to both the y-aminobutyric acid and benzodiazepine receptors and act as agonists at the active receptor sites.20... 

Recently, chloromethylated benzocoumarin 11c, hydroxylmethylated benzocou-marin 12, and chloromethylated coumarin 13 were used in the efficient preparation of several fluorescent ester conjugates of /V-benzyloxycarbonyl-neurotransmitter amino acids, such as p-alanine, tyrosine, 3,4-dihydroxyphenylalanine (DOPA), glutamic acid, and y-aminobutyric acid (GABA) [39, 40],... 

Amino acid There are 20 different amino acids that provide the building blocks of proteins. Three of them - aspartate, glutamate and glycine (together with GABA, or y-aminobutyric acid) also function as neurotransmitters. 

GABA (y-aminobutyric acid) The major inhibitory amino acid neurotransmitter of the CNS. 

In earlier studies the in vitro transition metal-catalyzed oxidation of proteins and the interaction of proteins with free radicals have been studied. In 1983, Levine [1] showed that the oxidative inactivation of enzymes and the oxidative modification of proteins resulted in the formation of protein carbonyl derivatives. These derivatives easily react with dinitrophenyl-hydrazine (DNPH) to form protein hydrazones, which were used for the detection of protein carbonyl content. Using this method and spin-trapping with PBN, it has been demonstrated [2,3] that protein oxidation and inactivation of glutamine synthetase (a key enzyme in the regulation of amino acid metabolism and the brain L-glutamate and y-aminobutyric acid levels) were sharply enhanced during ischemia- and reperfusion-induced injury in gerbil brain. 

In addition to a-allenic a-amino acids, the corresponding allenic derivatives of y-aminobutyric acid (GABA) have also been synthesized as potential inhibitors of the pyridoxal phosphate-dependent enzyme GABA-aminotransferase (Scheme 18.49) [131,138-142]. The synthesis of y-allenyl-GABA (152) and its methylated derivatives was accomplished through Crabbe reaction [131], aza-Cope rearrangement [138] and lactam allenylation [139], whereas the fluoroallene 153 was prepared by SN2 -reduc-tion of a propargylic chloride [141]. 

Amino acid derivatives include the thyroid hormones, catecholamines (e.g. adrenaline (epinephrine)) and dopamine, neurotransmitters such as y-aminobutyric acid (GABA) and noradrenaline (norepinephrine). All of these signalling molecules retain... 

Based on the idea that pyrrolidines can be metabolized selectively to y-aminobutyric acid derivatives, Wall and Baker [189] developed a retro-metabolic approach with 3-(4-chlorophenyl)pyrrolidine (5.92, Fig. 5.25) as a prodrug for the GABA-ergic agent baclofen (5.93, Fig. 5.25). In vitro studies showed that metabolism of 5.92 yields a pair of isomeric lactam metabolites (5.94, 5.96) and a pair of isomeric amino acid metabolites (5.93, 5.95). The formation of the metabolites resulting from the oxidation... 

The amino acid neurotransmitters are subdivided into primarily excitatory (glutamate, aspartate) and inhibitory (y-aminobutyric acid, GABA, glycine) types. 

The applicability of cinchonan carbamate CSPs for bioanalytical investigations using HPLC-ESI-MS/MS has been demonstrated by Fakt et al. [120]. The goal was the stereoselective bioanalysis of (R)-3-amino-2-fluoropropylphosphinic acid, a y-aminobutyric acid (GABA) receptor agonist, in blood plasma in order to determine whether this active enantiomer is in vivo converted to the 5-enantiomer. In this enantioselective HPLC-MS/MS bioassay, sample preparation consisted of... 

Xu M, Akabas MH. 1996. Amino acids lining the channel of the y-aminobutyric acid type A receptor identified by cysteine substitution. J Biol Chem 268 21505-21508. 

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