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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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.[1]


  1. Mechanism of cyanide inhibition of the blood-clotting, vitamin K-dependent carboxylase. Dowd, P., Ham, S.W. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
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