Vitamin K-dependent carboxylase: evidence for a hydroperoxide intermediate in the reaction.
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 two reactions (carboxylation and epoxidation) are coupled. Glutathione peroxidase, which reduces hydrogen peroxide and organic hydroperoxides, inhibits both of these reactions in a prepartion 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.
D000818:Animals; D019735:Carbon-Carbon Ligases; D002374:Catalase / Q000494:pharmacology; D004852:Epoxy Compounds / Q000378:metabolism; D005971:Glutamates; D005979:Glutathione Peroxidase / Q000494:pharmacology; D007700:Kinetics; D008025:Ligases / Q000378:metabolism*; D008862:Microsomes, Liver / Q000201:enzymology*; D010545:Peroxides; D011516:Prothrombin; D051381:Rats; D014812:Vitamin K / Q000031:analogs & derivatives / Q000494:pharmacology; D014813:Vitamin K Deficiency / Q000201:enzymology*
D004852:Epoxy Compounds; D005971:Glutamates; D010545:Peroxides; D014812:Vitamin K; D011516:Prothrombin; D002374:Catalase; D005979:Glutathione Peroxidase; D008025:Ligases; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase