The Chemistry and Enzymology of Bovine Factor X

Abstract

In the currently proposed schemes for blood coagulation [14,57,94], Factor X lies at the point of convergence of two distinguishable routes by which clotting is initiated. These two routes have been labeled the intrinsic and extrinsic coagulation pathways. Factor X exists in the plasma in an enzymatically inactive or zymogen form which, during coagulation, is activated to yield the proteolytic enzyme Factor Xa. Activation of Factor X via the intrinsic pathway requires only plasma-contained clotting factors, while the extrinsic pathway requires the participation of tissue-derived substances as well as plasma factors. The only known physiologic substrate for Factor Xa is another zymogen, prothrombin, which is activated to yield the protease thrombin. In turn, thrombin acts upon fibrinogen-yielding fibrin, which polymerizes to form a fibrin clot. Since the activation of Factor X is the first reaction common to both the intrinsic and extrinsic coagulation pathways, this activation process must be viewed as a key event in initiating thrombin formation as well as subsequent fibrin clot formation. Likewise, control of this activation process, as well as the consequent action of Factor Xa, becomes critical to regulating the formation and subsequent action of thrombin.A vitamin requirement for normal blood coagulation was first shown from the work of Dam [12], who named this vitamin "vitamin K." It was subsequently demonstrated that vitamin K was necessary for the formation of four specific plasma proteins, blood coagulation factors VII [52,77], IX [64,71,84], and X [3,42,84] in addition to prothrombin [89]. Of these proteins, in addition to Factor X itself, one is the substrate for Factor Xa, and the other two are responsible for Factor X activation.In the present discussion, we shall consider the isolation and characterization of Factor X, the process by which it is activated to yield Factor Xa, and finally the properties of Factor Xa as a proteolytic enzyme. This is not intended as a comprehensive review of all work in the field, but rather a presentation of what we believe to be salient features of Factor X chemistry and enzymology as well as recent developments in this field. The authors recognize that the development or our understanding of the chemistry and function of Factor X is the product of the contributions of many workers, some of whom may not be explicitly credited. We apologize for such omissions and would welcome their being called to our attention.