In vivo detoxification of cyanide by cystathionase γ-lyase

• Published in: Biochemical pharmacology 1996-09, Vol.52 (6), p.941-944
• Main Authors: Porter, Dale W., Nealley, Eric W., Baskin, Steven I.
• Format: Article
• Language: English
• Subjects: 3-mercaptopyruvate sulfurtransferase; Animals; Biological and medical sciences; Chemical and industrial products toxicology. Toxic occupational diseases; cyanide detoxification; Cyanides - metabolism; cystathionase γ-lyase; Cystathionine gamma-Lyase - pharmacology; Dose-Response Relationship, Drug; Liver - drug effects; Lyases - pharmacology; Male; Medical sciences; Metals and various inorganic compounds; Rats; Rats, Sprague-Dawley; rhodanese; thiocyanate; Toxicology
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/0006-2952(96)00466-2

The results of several in vitro studies have suggested that the enzyme cystathionase γ-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 γ-lyase is involved in the endogenous detoxification of cyanide, it logically follows that inhibiting cystathionase γ-lyase should increase the toxicity of cyanide. To test this hypothesis, the activity of cystathionase γ-lyase was inhibited with a suicide inhibitor, 2-amino-4-pentynoic acid (propargylglycine). The activity of liver cystathionase γ-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 ld 50 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 ld 50 of cyanide determined in control rats. The results of these studies suggest that cystathionase γ-lyase may participate in the detoxification of cyanide in vivo.