On the inhibition of glutamic acid decarboxylase and gamma-aminobutyric acid transaminase by sodium cyanide. 1991

G Cassel, and L Karlsson, and A Sellström
Department of NBC Defence, National Defense Research Establishment, Umeå, Sweden.

The effects of sodium cyanide (NaCN) on the gamma-aminobutyric acid metabolizing enzymes glutamic acid decarboxylase (GAD) and gamma-aminobutyric acid transaminase (GABA-T) were studied in vitro. With no pyridoxal-5-phosphate added, GAD was non-competitively inhibited by NaCN, with an IC50 of 280 microM. GAD was also inhibited when exposed to an equimolar amount of NaCN and pyridoxal-5-phosphate. NaCN inhibited GABA-T. The inhibition kinetics suggests that NaCN may react with more than one of the substrates and products present during the reaction, i.e. pyridoxal-5-phosphate, alpha-ketoglutarate and/or succinic semialdehyde. The presence of pyridoxal-5-phosphate in the reaction mixture completely protected GABA-T from inhibition by NaCN. The gamma-aminobutyric acid synthesizing enzyme, GAD may thus be inhibited in vivo by NaCN or by a reaction product of NaCN and pyridoxal-5-phosphate. The gamma-aminobutyric acid catabolizing enzyme, GABA-T is not as vulnerable to inhibition by NaCN, since the cyanide-pyridoxal-5-phosphate complex is ineffective as inhibitor.

UI MeSH Term Description Entries
D008297 Male Males
D011732 Pyridoxal Phosphate This is the active form of VITAMIN B 6 serving as a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. During transamination of amino acids, pyridoxal phosphate is transiently converted into pyridoxamine phosphate (PYRIDOXAMINE). Pyridoxal 5-Phosphate,Pyridoxal-P,Phosphate, Pyridoxal,Pyridoxal 5 Phosphate,Pyridoxal P
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005680 gamma-Aminobutyric Acid The most common inhibitory neurotransmitter in the central nervous system. 4-Aminobutyric Acid,GABA,4-Aminobutanoic Acid,Aminalon,Aminalone,Gammalon,Lithium GABA,gamma-Aminobutyric Acid, Calcium Salt (2:1),gamma-Aminobutyric Acid, Hydrochloride,gamma-Aminobutyric Acid, Monolithium Salt,gamma-Aminobutyric Acid, Monosodium Salt,gamma-Aminobutyric Acid, Zinc Salt (2:1),4 Aminobutanoic Acid,4 Aminobutyric Acid,Acid, Hydrochloride gamma-Aminobutyric,GABA, Lithium,Hydrochloride gamma-Aminobutyric Acid,gamma Aminobutyric Acid,gamma Aminobutyric Acid, Hydrochloride,gamma Aminobutyric Acid, Monolithium Salt,gamma Aminobutyric Acid, Monosodium Salt
D005968 Glutamate Decarboxylase A pyridoxal-phosphate protein that catalyzes the alpha-decarboxylation of L-glutamic acid to form gamma-aminobutyric acid and carbon dioxide. The enzyme is found in bacteria and in invertebrate and vertebrate nervous systems. It is the rate-limiting enzyme in determining GAMMA-AMINOBUTYRIC ACID levels in normal nervous tissues. The brain enzyme also acts on L-cysteate, L-cysteine sulfinate, and L-aspartate. EC 4.1.1.15. Glutamate Carboxy-Lyase,Glutamic Acid Decarboxylase,Acid Decarboxylase, Glutamic,Carboxy-Lyase, Glutamate,Decarboxylase, Glutamate,Decarboxylase, Glutamic Acid,Glutamate Carboxy Lyase
D000612 4-Aminobutyrate Transaminase An enzyme that converts brain gamma-aminobutyric acid (GAMMA-AMINOBUTYRIC ACID) into succinate semialdehyde, which can be converted to succinic acid and enter the citric acid cycle. It also acts on beta-alanine. EC 2.6.1.19. Aminobutyrate Aminotransferase,GABA Transaminase,beta-Alanine Ketoglutarate Aminotransferase,GABA Aminotransferase,GABA-alpha-Ketoglutarate Aminotransferase,4 Aminobutyrate Transaminase,Aminotransferase, Aminobutyrate,Aminotransferase, GABA,Aminotransferase, GABA-alpha-Ketoglutarate,Aminotransferase, beta-Alanine Ketoglutarate,GABA alpha Ketoglutarate Aminotransferase,Ketoglutarate Aminotransferase, beta-Alanine,Transaminase, 4-Aminobutyrate,Transaminase, GABA,beta Alanine Ketoglutarate Aminotransferase
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012966 Sodium Cyanide A highly poisonous compound that is an inhibitor of many metabolic processes and is used as a test reagent for the function of chemoreceptors. It is also used in many industrial processes. Cyanogran,Cyanide, Sodium
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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