On the inhibition of glutamic acid decarboxylase and gamma-aminobutyric acid transaminase by sodium cyanide.
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.
Cassel
G
G
Department of NBC Defence, National Defense Research Establishment, Umeå, Sweden.
Karlsson
L
L
Sellström
A
A
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005968:Glutamate Decarboxylase / Q000037:antagonists & inhibitors*; D008297:Male; D011732:Pyridoxal Phosphate / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012966:Sodium Cyanide / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005680:gamma-Aminobutyric Acid; D011732:Pyridoxal Phosphate; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase; D012966:Sodium Cyanide