Active site, viii

The initial steps of the intrinsic pathway are somewhat more complicated. This system requires the presence of clotting factors VIII, IX, XI and XII, all of which, except for factor VIII, are endo-acting proteases. As in the case of the extrinsic pathway, the intrinsic pathway is triggered upon exposure of the clotting factors to proteins present on the surface of body tissue exposed by vascular injury. These protein binding/activation sites probably include collagen. 

VIII.A. In Situ Investigations of Gas Solid Reactions and Active Sites. 196... 

Mechanism of action - Argatroban is a synthetic, direct thrombin inhibitor that reversibly binds to the thrombin active site. It inhibits thrombin-catalyzed or induced reactions, including fibrin formation activation of coagulation factors V, VIII, and XIII protein C and platelet aggregation. 

Platelet membrane phosphatidylserine is critical to the formation of the tenase complex since on its surface activated factor VIII (Villa) generates a high-afflnity binding site for activated factor IX (IXa) in the presence of calcium. Subsequently, this complex activates factor X (2, 13). Platelet membrane phosphatidylserine similarly anchors activated factor V (Va), favoring the calcium-dependent binding of activated factor X (Xa). The prothrombinase complex is generated on the surface of the anionic platelet membrane phosphatidylserine when factor Va binds prothrombin. The prothrombinase complex cleaves prothrombin to produce thrombin, which has a multifunctional role (14). 

Numerous oxo-molybdo-bis(dithiolene) and oxo-tungsto-bis(dithiolene) complexes have been synthesized and characterized as potential structural analogues of the active sites of the dimethyl sulfoxide reductase (DMSOR) and aldehyde oxidoreductase (AOR) families of mononuclear Mo and W enzymes [see Fig. 16 and Chapter 10 in this volume (50)]. The available IR and Raman data for the Mo and W complexes are summarized in Tables VII and VIII,... 

In the polymerization of ethylene by (Tr-CjHsljTiClj/AlMejCl [111] and of butadiene by Co(acac)3/AlEt2Cl/H2 0 [87] there is evidence for bimolecular termination. The conclusions on ethylene polymerization have been questioned, however, and it has been proposed that intramolecular decomposition of the catalyst complex occurs via ionic intermediates [91], Smith and Zelmer [275] have examined several catalyst systems for ethylene polymerization and with the assumption that the rate at any time is proportional to the active site concentration ([C ]), second order catalyst decay was deduced, since 1 — [Cf] /[Cf] was linear with time. This evidence, of course, does not distinguish between chemical deactivation and physical occlusion of sites. In conjugated diene polymerization by Group VIII metal catalysts -the unsaturated polymer chain stabilizes the active centre and the copolymerization of a monoolefin which converts the growing chain from a tt to a a bonded structure is followed by a catalyst decomposition, with a reduction in rate and polymer molecular weight [88]. 

Catalysts from Group VIII metals have given unsatisfactory results. In the polymerization of butadiene with soluble cobalt catalysts tritium is not incorporated when dry active methanol is employed [115], although it is combined when it has not been specially dried [117, 118]. Alkoxyl groups have been found when using dry alcohol [115, 119] but the reaction is apparently slow and not suited to quantitative work [119]. Side reactions result in the incorporation of tritium into the polymer other than by termination of active chains [118], probably from the addition of hydrogen chloride produced by reaction of the alcohol with the aluminium diethyl chloride [108], Complexes of nickel, rhodium and ruthenium will polymerize butadiene in alcohol solution [7, 120], and with these it has not been possible to determine active site concentrations directly. 

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