In vivo detoxification of cyanide by cystathionase gamma-lyase.
The results of several in vitro studies have suggested that the enzyme cystathionase gamma-lyase (EC 4.4.1.1) may function in the endogenous detoxification of cyanide; however, this possibility has not been investigated in vivo. If cystathionase gamma-lyase in involved in the endogenous detoxification of cyanide, it logically follows that inhibiting cystathionase gamma-lyase should increase the toxicity of cyanide. To test this hypothesis, the activity of cystathionase gamma-lyase was inhibited with a suicide inhibitor, 2-amino-4-pentynoic acid (propargyl-glycine). The activity of liver cystathionase gamma-lyase activity was decreased 96.8% by administration of propargylglycine, indicating that the propargylglycine treatment was effective. The propargylglycine treatment did not alter the activity of thiosulfate:cyanide sulfurtransferase (EC 2.8.1.1) or 3-mercaptopyruvate:cyanide sulfurtransferase (EC 2.8.1.2), two other enzymes that have been proposed to be involved in the detoxification of cyanide. The LD50 of cyanide in rats treated with propargylglycine was 5.14 +/- 0.029 mg NaCN/kg, which was significantly (P < 0.05) lower than the 5.98 +/- 0.008 mg NaCN/kg LD50 of cyanide determined in control rats. The results of these studies suggest that cystathionase gamma-lyase may participate in the detoxification of cyanide in vivo.
Porter
D W
DW
Biochemical Pharmacology Branch, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425, USA.
Nealley
E W
EW
Baskin
S I
SI
D000818:Animals; D003486:Cyanides / Q000378:metabolism*; D003542:Cystathionine gamma-Lyase / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects*; D008190:Lyases / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D003486:Cyanides; D008190:Lyases; D003542:Cystathionine gamma-Lyase