Vitamin K-dependent carboxylase: evidence for a hydroperoxide intermediate in the reaction.

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Abstract
Vitamin K is an essential cofactor for a microsomal carboxylase that converts glutamyl residues in endogenous precursor proteins to .gamma.-carboxyglutamyl residues in completed proteins. The same microsomal preparations convert vitamin K to its 2,3-epoxide, and it has been suggested that these 2 reactions (carboxylation and epoxidation) are coupled. Glutathione peroxidase [from rat liver], which reduces hydrogen peroxide and organic hydroperoxides, inhibits both of these reactions in a preparation of microsomes solubilized by Triton X-100. Catalase has no effect. In the absence of vitamin K, and in the presence of NADPH, tert-butyl hydroperoxide acts as a weak vitamin K analog. At lower concentrations, tert-butyl hydroperoxide is an apparent competitive inhibitor of vitamin K for both the carboxylase and epoxidase reactions. These data are consistent with the hypothesis that both of these vitamin K-requiring reactions involve a common oxygenated intermediate, and that a hydroperoxide of the vitamin is the species involved.