RT Journal Article ID 7a458fb55067321e A1 Kalafatis, Michael A1 Egan, Jack O. A1 van't Veer, Cornells A1 Mann, Kenneth G. T1 Regulation and Regulatory Role of γ-Carboxyglutamic Acid Containing Clotting Factors JF Critical Reviews™ in Eukaryotic Gene Expression JO CRE YR 1996 FD 1996-03-30 VO 6 IS 1 SP 87 OP 101 K1 membrane surface K1 carboxylase K1 complex formation K1 α-thrombin. AB Blood coagulation is initiated following damage of the vessel wall. The large number of proteins that participate in the reactions that regulate blood coagulation must behave in a concerted manner to generate α-thrombin. This most abundant enzyme product of the coagulation process acts on the soluble blood protein fibrinogen to create the insoluble fibrin clot, trigger platelet activation, and initiate a variety of vascular processes ranging from coagulation inhibition and activation of fibrinolysis to cell growth. The majority of enzymes that participate in the blood-clotting process circulate in blood as inactive zymogens and procofactors. Following mechanical injury to the vessel wall, a cell-associated protein, tissue factor, is exposed and initiates a series of enzymatic reactions localized on a membrane surface generally provided by cells and accumulating platelets. The binding of the enzymes and zymogen substrates to the exposed membrane surface and their activation are in part governed by the γ-carboxyglutamic acid residues (gla) of each protein. Recently, it has been demonstrated that the gla residues are necessary for Ca2+ binding and subsequent exposure of the hydrophobic membrane binding regions to the cell bilayer. Thus, the gla residues play a preeminent role during the blood-clotting process. Absence of γ-carboxylation of one or more of the critical glutamic acid residues results in an impaired coagulation/anticoagulation process which may lead to a bleeding diathesis or thrombosis. PB Begell House LK https://www.dl.begellhouse.com/journals/6dbf508d3b17c437,4e5dc78f6cfef1b9,7a458fb55067321e.html