Factor VIIa: Difference between revisions

FVIIa alone shows very little proteolytic activity and only becomes fully active when complexed to its obligatory cofactor, tissue factor (TF) and cations (mainly Ca++) <ref>PMID:1537862</ref><ref>PMID:18640965</ref>. TF, located in the vessel wall, is exposed to circulating FVIIa upon injury or some type of stimulus and forms a TF-FVIIa complex. A unique property of TF-FVIIa among other coagulation enzyme complexes is that phospholipids are not an obligate requirement for the assembly of the complex<ref>PMID:1537862</ref>. However, the activity of the complex towards its substrates (FIX and FX) requires a lipid surface which is provided by the anchoring of TF to a cell membrane. The TF-phospholipid complex enhances the efficiency (kcat/Km) of FVIIa-catalyzed reactions by the 107-fold6. Analysis of data utilizing small non-lipid FVIIa binding fluorescent substrates and the natural substrate FX suggest that the phsopholipids do not directly influence the catalytic activity of the complex but enhance FX substrate proteolysis. Possible mechanisms may include cell surface binding concentration effects and induced changes in FX upon binding to the membrane6,9. There are four distinct steps that are required for the full activity of the TF-FVIIa complex Scheme 1: 1) proteolytic activation of single-chained FVII to two-chain disulfide bridged FVIIa 2) binding of Ca++ which is essential for the activity of the protease 3) interaction of TF with FVIIa which increases substrate turnover (kcat) but not substrate affinity (Km) and 4) acidic-membrane association and proper orientation of substrate.