Mechanism of cyanide inhibition of the blood-clotting, vitamin K-dependent carboxylase.
Cyanide is a competitive inhibitor of carbon dioxide in the vitamin K-dependent glutamate carboxylase system, which plays a central role in the function of the blood clotting cascade. The mechanism of cyanide inhibition has been obscure for some time. At pH 7.2, cyanide (pKa = 9.21) will exist in solution as hydrogen cyanide to the extent of 99%. Hydrogen cyanide is linear triatomic molecule able to serve as a surrogate for carbon dioxide at the enzyme active site. Hydrogen cyanide is an acid; it will quench the deprotonated glutamate carbanion precursor to gamma-carboxyglutamate, resulting in inhibition of the carboxylation sequence.
Dowd
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Department of Chemistry, University of Pittsburgh, PA 15260.
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D000595:Amino Acid Sequence; D001777:Blood Coagulation; D019735:Carbon-Carbon Ligases; D006801:Humans; D007700:Kinetics; D008025:Ligases / Q000037:antagonists & inhibitors*; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D011190:Potassium Cyanide / Q000494:pharmacology*; D014316:Tritium
D009842:Oligopeptides; D014316:Tritium; D008025:Ligases; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase; D011190:Potassium Cyanide