tissue factor (TF) + factor VII (F7) -> TF:F7 complex

Stable Identifier
R-HSA-140783
Type
Reaction
Species
Homo sapiens
Compartment
Synonyms
formation of TF:F7 complex
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Coagulation factor VII circulates in plasma mostly in the zymogen form (FVII); about 1% of plasma FVII is found in the active form (FVIIa) (Morrissey JH et al. 1993). Initiation of coagulation begins by exposure of blood (which contains both zymogen FVII and activated FVIIa) to tissue factor (TF) in the extravascular space at an injury site and formation of the Ca2+-dependent complex between TF and plasma FVII/FVIIa (Kelley RF et al. 2004; Ruf W et al. 1991). The TF:FVII zymogen complex has low but measurable proteolytic activity on factor X, suggesting that this complex initiates TF-dependent clotting through a minimal generation of factor Xa, which in turn catalyzes the activation of FVII from plasma. (Rao LV et al. 1986). As factor VIIa accumulates, TFr:FVIIa complexes also form, accelerating the process (Nemerson 1988). Formation of the TF:FVIIa complex greatly increases the enzymatic activity of FVIIa via allosteric interactions between TF and FVIIa, as revealed by a 20- to 100-fold increase in the rate of amidolysis of small, chromogenic peptidyl substrates (Broze GJ Jr & Majerus PW.1980; Butenas S et al. 1994; Higashi S et al. 1996). A second model, building on the observation that normal plasma contains low levels of activated FVIIa constitutively, suggests that complexes with FVIIa form immediately at the onset of clotting (Rapaport and Rao 1995). The two models are not mutually exclusive, and in any event, the central roles of TF and FVIIa in generating an initial supply of factors IXa and Xa, and the self-limiting nature of the process due to the action of TFPI, are all well-established.

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