The effect of sodium tetrathionate on cyanide conversion to thiocyanate by enzymatic and non-enzymatic mechanisms.
Sodium tetrathionate has been proposed as a cyanide antidote despite its reported toxicology and inhibitory effect on rhodanese. We investigated the effect of tetrathionate and an analog, dithionite, on rhodanese activity because of their structural similarity to thiosulfate, a known sulfane sulfur donor for this enzyme. Rhodanese activity of guinea pig liver homogenate was assayed by measuring the formation of ferric thiocyanate complex at 460 nm. With thiosulfate as a substrate, the Km for rhodanese was 6.7 mM and the Vmax was 0.67 mumol thiocyanate min-1 mg-1 protein. The conversion of cyanide to thiocyanate by rhodanese was inhibited in the presence of tetrathionate at the millimolar concentration (e.g. 1 mM) range. Dithionite had a negligible effect on rhodanese activity. Neither thiosulfate (1-100 mM) nor dithionite produced significant amounts of thiocyanate from cyanide spontaneously (i.e. non-enzymatically). However, in the absence of rhodanese, tetrathionate (1.0, 10.0 and 100.0 mM) produced a dose-dependent increase in thiocyanate. These data suggest that tetrathionate detoxifies cyanide non-enzymatically, which may, in part, account for its antidotal effects.
Baskin
S I
SI
Pharmacology Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425.
Kirby
S D
SD
D000818:Animals; D003486:Cyanides / Q000378:metabolism*; D004227:Dithionite / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D013776:Tetrathionic Acid / Q000494:pharmacology*; D013861:Thiocyanates / Q000378:metabolism*; D013884:Thiosulfate Sulfurtransferase / Q000378:metabolism; D013885:Thiosulfates / Q000494:pharmacology
D003486:Cyanides; D013861:Thiocyanates; D013885:Thiosulfates; D004227:Dithionite; D013776:Tetrathionic Acid; D013884:Thiosulfate Sulfurtransferase