title: Incomplete gamma carboxylation of human coagulation factor VII: differential effects on tissue factor binding and enzymatic activity.
abstract: The integrity of the gamma-carboxylic glutamic acid (GLA) residues of coagulation factor VII are thought to be essential for both the interaction of factor VII with its cell-surface lipoprotein receptor tissue factor and for the activated protein to manifest its serine protease activity. During the course of transiently expressing recombinant human factor VII in monkey COS cells it was noted that the factor VII synthesized in the absence of added vitamin K had <20% of expected procoagulant activity yet retained 65% of its binding activity to recombinant human tissue factor. Similar results were obtained when vitamin K was omitted from human 293 cell cultures permanently expressing recombinant factor VII. In contrast, both transient and permanent expression of factor VII in human 293 cell cultures containing physiological concentrations of vitamin K resulted in the synthesis of fully functional factor VII. Furthermore, factor VII in plasma samples from 24 patients undergoing warfarin therapy bound quantitatively to tissue factor whereas factor VII procoagulant activity averaged 65% of normal. Thus, data from both in vitro and in vivo situations indicated that factor VII molecules with suboptimal GLA content retained most of their ability to bind tissue factor but exhibited reduced procoagulant activity.
authors.affiliation: Department of Pathology, McMaster University, Hamilton. Ontario, Canada.
authors.forename: B J
authors.initials: BJ
authors.lastname: Clarke
authors.forename: S
authors.initials: S
authors.lastname: Sridhara
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D005167:Factor VII / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism*; D014812:Vitamin K / Q000494:pharmacology; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D014812:Vitamin K; D014859:Warfarin; D005167:Factor VII; D013925:Thromboplastin; D012697:Serine Endopeptidases