Vitamin K-dependent carboxylase: Increased activity in a hypoprothrombinemia state

Abstract

Rat liver microsomes contain a vitamin K-dependent carboxylase activity that converts protein-bound glutamyl residues to γ-carboxy glutamyl residues. This activity has been studied utilizing low molecular weight peptides (peptide carboxylase) and endogenous microsomal precursor proteins (protein carboxylase) as substrates for the enzyme. Feeding rats a vitamin K-deficient diet or the administration of Warfarin, causes a 2- to 3-fold increase in these activities. The increase in peptide carboxylase activity is not dependent on the presence of increased amounts of prothrombin precursors in the microsomes and is more closely correlated with the degree of plasma hypoprothrombinemia than with the level of these precursors in the liver. The protein carboxylase activity appears to reflect the level of precursor substrates in the liver. The apparent induction of peptide carboxylase activity is not due to an alteration in affinity of the enzyme for its substrate. An apparent rapid turnover of the enzyme complicated the interpretation of experiments which utilized the protein synthesis inhibitor cycloheximide. The data were, however, consistent with the hypothesis that the increased activity measured represents a synthesis of an increased amount of enzyme rather than an activation of existing inhibited activity.