EVIDENCE FOR COMPETITION BETWEEN VITAMIN-K-DEPENDENT CLOTTING FACTORS FOR INTRACELLULAR PROCESSING BY THE VITAMIN-K-DEPENDENT GAMMA-CARBOXYLASE

This study demonstrates an apparent competition between newly synthesized precursors of prothrombin and factor X for binding to and processing by the gamma-carboxylase in the ER membrane of hepatocytes. The precursor of factor X appears to exhibit a stronger affinity for the carboxylase than the prothrombin precursor. This conclusion is supported by the findings that 1) in normal hepatocytes, the factor X precursor prevents increased prothrombin precursor binding to the ER membrane, 2) increased prothrombin binding to the ER membrane was measured in H4-II-E-C3 Reuber H-35 cells where factor X synthesis is suppressed. The variations in the concentrations of the prothrombin and the factor X precursors that were associated with the ER membrane correlated with the available prothrombin and factor X substrate pools for the gamma-carboxylase.