Effect of [beta], [beta]'-iminodipropionifrile on [gamma]-aminobutyric acid content, [gamma]-aminobtyric acid-[alpha]-ketoglutaric acid transaminase and aromatic amoni acid transaminases
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[beta], [beta]'-iminodipropionitrile (IDPN), a synthetic aminonitrile similar to those isolated from Lathyrus odoratus, has been shown to produce a permanent neurological syndrome in a wide variety of animals. Pathological changes have been observed in the central nervous system of animals treated with IDPN. At present very little is known about the metabolic effect of IDPN in the nervous system. Failure of its interference with catecholamines has been shown since nor-adrenaline content of the cerebral tissues of rats and mice injected with IDPN remains ec;, unaltered, while motor excitation syndromes were developed. Similarly, no change in the contents of aspartic acid, gamma-aminobutyric acid, threonine, glutamic acid and glutamine were observed in rat brains under similar experimental conditions. In order to elucidate the biochemical mechanism of action of IDPN, attempts were made to correlate in vivo studies with in vitro enzyme inhibition. The effect of IDPN on levels of GABA was studied by measuring the concentration of GABA after administration of IDPN. Similarly, in vivo effects of IDPN on GABA-T were also investigated. Little knowledge about aromatic amino acid transaminases and their role in the central nervous system activity prompted us to study the effect of IDPN on such transaminase systems operating in the brain. Glutamic acid and GABA have been shown to play an important role in the activity of the central nervous system. The involvement of transamination of aromatic amino acids in mental diseases, such as phenylpyruvic oligophrenia has also been reported. It has been suggested that such transamination may possibly compete with available amino = acids during the synthesis of biological active amines. Determination of GABA was essentially carried out as described by Baxter (1961). GABA content in the rat brain gray matter was determined enzymatically after its extraction with alcohol. The assay method is coupled to TPN+ reduction where GABA is converted to succinate via transamination and oxidation. Assays for GABA-T were conducted in a soluble enzyme preparation from acetone powder by the method described by Baxter and Roberts (1958). The enzyme activity was measured by determinating the amount of glutamic acid formed. Studies with aromatic amino acid transaminases and their enzymatic assays were following the method of Haavaldsen et al. (1964, 1965). The assay is based on the ability of the enol tautomers of aromatic keto acids, produced from the transaminations of aromatic amino acids, to form cqmplexes with borate which showed characteristic absorption spectra in the 300 mu region [TRUNCATED]
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