1 -Aminobutyric acid

Dent ISS) reported the appearance of this amino acid in the urine of a patient with hepatic disease following the administration of large amounts of methionine. Lien and Greenberg (68) have shown that it is formed from threonine, and Matsuo and Greenberg that it is formed from methionine and homoserine (ISS) in the animal body. More recent studies established that a-ketobutyiic add, the precursor of a-aminobutyric acid, is a product of the enzymic deavage of threonine, homoserine, and cystathionine (see Section IV). 

The L-form of the amino acid is comparatively slowly transaminated by heart muscle (76), the D-form is oxidized by D-amino acid oxidase (iS9). It was shown to be antiketogenic by Cohen (79). 

Upon incubating DL-a-aminobutyric-3-O acid with rat liver homogenate, radioactive a-ketobutyric add and propionic acid were isolated by column chromatography on a silica gd colunm (140). The catabolism of this amino acid can be represented by the reactions of Fig. 8. 

Norvaline is strongly ketogenic (79). The L-form is attacked by L-amino acid oxidase (77) and the D-form by D-amino add oxidase (1S9). Its susceptibility to transamination has not been reported. Hassan and Greenberg (1S6) demonstrated that it is readily oxidized to COt in the intact animal. More of this amino add is excreted unchanged in the urine than is leudne. 

DL-Norvaline-3-C on administration to rats or on incubation with rat liver homogenates yielded radioactive a-ketovaleric acid, butyric acid, acetic acid, acetoacetate, and 3-hydroxybutyric acid HI). These compounds were isolated by column cluomatography and their identity established. Degradation of the butyric acid demonstrated that only C-2 was significantly labeled. This established that the butyrate was formed by a direct pathway from norvaline and not by the subsequent condoisation of two-carbon fragments. 

In 1957 widespread interest was roused by the report of Bazemore, Elliott and Florey that the Factor I activity of mammalian brain was due to its contained GABA. Since then a mass of information concerning the pharmacological actions of GABA has been collected it has been well reviewed on a number of occasions - .  

Whatever the actual composition of Factor /, it is undeniable that the brain contains large amounts of GABA and that the properties of this substance are inhibitory in nature. The neuropharmacology of GABA itself is therefore considered in this section. 

Some recent observations have underlined the necessity of interpreting with caution the results of experiments which have sought to modify GABA metabolism. Animals habituated to, and then withdrawn from, barbiturate drugs, develop (as do human beings) spontaneous convulsions or an increased susceptibility to audiogenic seizures . It was shown by Essig that these 

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See also g-Aminobutyric acid.) PYRROLE AND PYRROLE DERIVATIVES] (Vol 20)... 

COALCONVERSIONPROCESSES - CLEANING AND DESULFURIZATION] (Vol 6) Gamma-aminobutyric acid (GABA)... 

Lindane is used predominately as a seed dressing and soil insecticide, for the control of ectoparasites of humans and domestic animals, for the control of locusts and grasshoppers, and as a residual spray to control the Anopheles vectors of malaria. Because of its relatively high volatility it is useful to control wood-boring insects of timber, fmit trees, and ornamental plants. The mode of action is not well understood but is thought to be competitive blocking of the y-aminobutyric acid (GABA) transmitter of synaptic nerve transmission. 

Mode of Motion. The cyclodienes, like lindane and toxaphene, affect the nerve axon produciag hyperactivity, convulsions, prostration, and death. The biochemical lesion is the competitive inhibition of the y-aminobutyric acid (GABA) neurotransmitter binding site of the nerve axon. Spray workers with lengthy exposure to dieldrin have suffered from prolonged and repeated central nervous system disturbances produciag epileptiform coavulsioas. Similar disturbances occurred ia workers heavily exposed to chlordecoae. 

Avermectins and Ivermectin. The avermectias are pentacycHc lactones isolated from fermentation products of Streptomjces avermitilis and ivermectin is a semisynthetic chemical, 22,23-dihydroavermectia (46). Ivermectin is effective in very low doses for the control of red spider mites on deciduous fmits, in baits for the control of imported fire ants, and as a parasiticide for Onchocerca volvulus in humans and for catde gmbs. These insecticides appear to function as agonists for the neuroinhibitory transmitter y-aminobutyric acid (GABA) (see Antiparasitic agents, avermectins). 

Strong acids or bases catalyze the hydrolysis of 2-pyrrohdinone to 4-aminobutanoic acid [y-aminobutyric acid [56-12-2] (GABA)]. GABA is involved in the functioning of the brain and nervous system and is of considerable interest as a potential dietary supplement (60). 

Picrotoxin has been instmmental in estabUshing an inhibitory neurotransmitter role for the amino acid, gamma-aminobutyric acid (GABA), quantitatively the most important inhibitory neurotransmitter in the mammalian CNS. Whereas glycine is predominately localized in the spinal cord, GABA... 

Fig. 9. Stmcture of nisin where Dha = dehydroalanine Dhb = dehydrobutyrine Abu = a-aminobutyric acid Ala-S-Ala = me50-lanthionine and Abu-S-Ala = t/ireo-methyllanthionine. The first amino acid residue (Ala or Abu) of the lanthionine or methyUanthionine is a D residue all other amino...

MeVal = A-methylvaline and Abu = a-aminobutyric acid. The dotted lines indicate hydrogen bonds. 

Another class of therapeutic agents is used for the treatment of certain genetic diseases or other enzymatic disorders caused by the dysfunction or absence of one particular enzyme. This often leads to an unwanted accumulation or imbalance of metaboUtes in the organism. Eor example, some anticonvulsive agents are inhibitors for y-aminobutyric acid aminotransferase [9037-67-6]. An imbalance of two neurotransmitters, glutamate and y-aminobutyric acid, is responsible for the symptoms. Inhibition of the enzyme leads to an increase of its substrate y-aminobutyric acid, decreasing the imbalance and subsequently relieving the symptoms of the disease. 

Aminobutyric acid [2835-82-7] M 103.1, m 193-194 , pKeskd-3.5, pKEst(2)-10.3. Crystd form aqueous EtOH or MeOH -I- Et20. 

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