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 strong 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 as associated with the ER membrane correlated with the available prothrombin and factor X substrate pools for the gamma-carboxylase.
Stanton
C
C
National Dairy Products Research Center Morepark, Fermoy, Cork, Ireland.
Ross
P
P
Hutson
S
S
Wallin
R
R
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001483:Base Sequence; D015153:Blotting, Western; D002262:Carboxy-Lyases / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D005170:Factor X / Q000096:biosynthesis* / Q000187:drug effects; D008114:Liver Neoplasms, Experimental; D008969:Molecular Sequence Data; D011516:Prothrombin / Q000096:biosynthesis* / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014407:Tumor Cells, Cultured; D014812:Vitamin K / Q000378:metabolism*; D014859:Warfarin / Q000494:pharmacology
D000925:Anticoagulants; D012333:RNA, Messenger; D014812:Vitamin K; D014859:Warfarin; D011516:Prothrombin; D005170:Factor X; D002262:Carboxy-Lyases