Clotting factor VII

Strancar, A., Barut, M., Podgomik, A., Koselj, P, Schwinn, H., Raspor, P, and Josic, D., Application of compact porous tubes from preparative isolation of clotting factor VII from human plasma, /. Chromatogr. A, 760, 117, 1997. 

The mechanism of action of warfarin becomes apparent from the molecular details of the blood clotting process. The clotting factors VII, IX, and X require Ca ions for maximum activity. These proteins possess a novel amino acid which binds Ca ions. It is a modified form of the amino acid glutamate, as y-carboxyglutamate (Gla) which possesses two... 

Oral contraceptives have also been reported to produce increases in sulfobromophthalein retention and other liver function tests, as well as in prothrombin time, clotting factors VII, VIII, IX, serum thyroxine, and protein-bound iodine (B8). In a group of 48 women the mean cholesterol value was 206 41 mg/100 ml while they were receiving a variety of oral contraceptives and 179 28 mg/100 ml when they were not receiving the drugs (W19). 

The most obvious effect of a deficiency in vitamin K in animals is delayed blood clotting, which has been traced to a decrease in the activity of prothrombin and of clotting factors VII, IX, and X (Chapter 12, Fig. 12-17). Prothrombin formed by the liver in the absence of vitamin K lacks the ability to chelate calcium ions essential for the binding of prothrombin to phospholipids and to its activation to thrombin. The structural differences between this abnormal protein and the normal prothrombin have been pinpointed at the N terminus of the 560 residue glycoprotein.e f Tryptic peptides from the N termini differed in electrophoretic mobility. As detailed in Chapter 12, ten residues within the first 33, which were identified as glutamate residues by the sequence analysis on normal prothrombin, are actually y-carboxyglutamate (Gla). The same amino acid is present near the N termini of clotting factors VII, IX, and X. 

Morrill, P. R., Gupta, G., Sproule, K., et al. (2002) Rational combinatorial chemistry-based selection, synthesis and evaluation of an affinity adsorbent for recombinant human clotting factor VII. J. Chromatogr. B 774, 1-15. 

Heparin acts by binding to anti thrombin III, which serves as a major inhibitor of serine protease clotting enzymes. Abruptly ending heparin treatment can be hazardous because of reduced levels of antithrombin III. Coumarins, typified by warfarin, are structurally similar to vitamin K, which plays an important role in blood coagulation. By interfering with the function of vitamin K, vitamin K-dependent proteins such as clotting factors VII, IX, X and prothrombin are reduced. 

Thromboembohc events in relation to activated prothrombin complex products include deep venous thrombosis and pulmonary embohsm (3-5). So far, the exact mechanism of how thromboembohc events are stimulated by prothrombin complex products is not known. It has been postulated that the presence of activated clotting factors VII, IX, and X, as weU as procoagulatory phosphohpids in prothrombin complex products, are responsible (6). 

Fukase, K, Hase, S, Ikenaka, T, Kusumoto, S, Synthesis of new serine-linked oligosaccharides in blood-clotting factors VII and IX and protein Z. The syntheses of 0-a-D-xylopyranosyI-(l— 3)-d-glucopyranose, 0-a-D-xyIopyranosyl-( 1 — 3)-0-a-D-xylopyranosyl-( 1 — 3)-D-glucopyranose, and their conjugates with serine. Bull. Chem. Soc. Jpn., 65, 436-445, 1992. 

Vitamin K is critical to (he formation of clotting factors VII. IX. and X. These factors are glycoproteins that h.avc y-vaiboxyglutamic acid residues at the N-terminal end of (he ptptide chain. The enzyme involved in forming an active prothrombin is a vitamin K-dcpendcn( carboxyla.se located in the microsomal fraction of liver cells. It has been sug-... 

Vitamin K is used to synthesize prothrombin and clotting factors VII, IX, and X, and is an antidote for oral overdose of anticoagulant. Vitamin K is in leafy green vegetables, liver, cheese, and egg yolk, and is synthesized by intestinal flora. 

Vitamin K is used to synthesize prothrombin and clotting factors VII, IX, and X and is an antidote for oral overdose of anticoagulant. 

In general, the Factor VII activity estimated by a substrate assay correlated well with Factor VII activity determined by a clot-endpoint assay (P4, S13). However, some differences have been seen. Activation of Factor VII by kaolin or by exposure to cold temperatures (2-8°C) increased the level of clotting Factor VII by 4-7 times but bad no effect on the amount detected by the substrate assay (S9, TIO). It has been postulated that the partially carbox-ylated molecules of Factor VII present in patients plasma during anticoagulant therapy are detected by a substrate assay but not in a clot-endpoint test (P4). These differences between the two assay systems have been used to screen for hereditary Factor VII deficients and to detect the presence of Factor Vila in thrombotic disorders and in components for transfusion therapy (S13). 

---