Modifiers of mercaptopyruvate sulfurtransferase catalyzed conversion of cyanide to thiocyanate in vitro.
The enzyme mercaptopyruvate sulfurtransferase appears to play an important role in the in vivo detoxification of cyanide. It does so by transferring sulfur to cyanide to produce thiocyanate, which is less toxic and may be excreted through the kidney. Several compounds were tested for their ability to affect the rate of enzyme catalyzed thiocyanate formation in vitro. The studies were carried out using both a partially purified bovine kidney extract and a highly purified enzyme preparation. Hypotaurine and methanesulfinic acid doubled sulfurtransferase activity in the partially purified extract at 30 mM, but inhibited the purified enzyme to 57% (hypotaurine) and 27% (methanesulfinic acid) of control activity at the same concentration. Pyruvate, phenylpyruvate, oxobutyrate, and oxoglutarate each inhibited the extract and purified forms of mercaptopyruvate sulfurtransferase. Phenylpyruvate was the most effective inhibitor, reducing activity to 0.2% of control values in the extract, and 11% of control values for purified MPST when added to the reaction at 30 mM. Other compounds tested (see Table 1) had a negligible effect on sulfurtransferase activity. A heat stable cofactor was found in boiled kidney extract which stimulated sulfurtransferase activity in the extract but inhibited sulfurtransferase activity in the purified enzyme, as was observed for hypotaurine and methanesulfinate. The boiled extract had no thiocyanate forming activity of its own. The cofactor operated in synergy with methanesulfinate, but independently of hypotaurine.
Wing
D A
DA
Pharmacology Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010.
Baskin
S I
SI
D002384:Catalysis; D003486:Cyanides / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D010667:Phenylpyruvic Acids / Q000494:pharmacology; D011773:Pyruvates / Q000494:pharmacology*; D013441:Sulfinic Acids / Q000494:pharmacology*; D013466:Sulfurtransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013861:Thiocyanates / Q000378:metabolism*; D014020:Tissue Extracts
D003486:Cyanides; D010667:Phenylpyruvic Acids; D011773:Pyruvates; D013441:Sulfinic Acids; D013861:Thiocyanates; D014020:Tissue Extracts; C053310:methanesulfinic acid; D013654:Taurine; C003949:hypotaurine; C008366:3-mercaptopyruvic acid; D013466:Sulfurtransferases; C021550:3-mercaptopyruvate sulphurtransferase; D003545:Cysteine; C031606:phenylpyruvic acid