Prothrombin precursor

Immunoglobulin Melanoma-associated antigen Pancreas-associated antigen Pregnancy-specific protein 1 Prothrombin precursor Tumorr-associated trypsin inhibitor... 

Cattle receiving vitamin K antagonists synthesize a prothrombin precursor with identical amino acid and carbohydrate composition, and immunological properties, but with markedly reduced affinity for calcium. Thus, while normal prothrombin binds four Ca ions, the prothrombin elaborated in absence of vitamin K can bind only one Ca ion. Normal prothrombin contains an unidentified prosthetic group that is absent from the polypeptide chain in vitamin K deficient prothrombin. A peptide containing the vitamin K moiety has been prepared from normal prothrombin [54-58]. 

Zymogen is a precursor protein that is converted to an active protease when one or more of its peptide bonds are cleaved. Zymogens involved in coagulation include factors II (prothrombin), VII, IX, X, and XI. 

Prothrombin and several other proteins of the blood clotting system (Factors VII, IX and X, and proteins C and S) each contain between four and six y-carboxygluta-mate residues which chelate calcium ions and so permit the binding of the blood clotting proteins to membranes. In vitamin K deficiency or in the presence of warfarin, an abnormal precursor of prothrombin (preprothrombin) containing little or no y-carboxyglutamate, and incapable of chelating calcium, is released into the circulation. 

Pmrl Proteinase K Prothrombin fatty acids (378,379) Yeast Golgi Ca2+/Mn2+-ATPase ion pump (380,381) Peptide fragmentation enzyme (382) Thrombin precursor extracellular trigger involved in blood clotting... 

II Prothrombin Both Precursor of thrombin, which activates factors I, V, VII, VIII and XIII... 

In normal individuals phytonadione and the menaquinones have no activity while in vitamin K deficiency the vitamin promotes the hepatic biosynthesis of factor II (prothrombin), factor VII, factor IX and factor X. Vitamin K functions as an essential cofactor for the enzymatic activation of precursors of these vitamin K dependent clotting factors. The quinone structure of the active form of vitamin K, i.e. reduced vitamin K or hydroquinone. 

PRECURSOR. In biological systems, an intermediate compound or molecular complex present in a living organism which, when activated physiochemically, is converted to a specific functional substance. Sometimes the prefix pro is used to indicate that a compound in question plays the role of a precursor. Examples from the history of vitamin and other essential chemical developments include ergosterol (pro-vitamin D2), which is activated by ultraviolet radiation to form vitamin D carotene (provitamin A) is a precursor of vitamin A prothrombin forms thrombin upon activation in the blood-clotting mechanism. 

Thrombin cannot be allowed to circulate freely in the blood, but must be produced rapidly when clotting is initiated. Thrombin is derived from its inactive precursor, prothrombin, in a cascade of reactions in which a sequence of inactive factors is activated each factor activates the next by proteolytic cleavage. The whole process is initiated by exposure of blood to an abnormal surface, such as collagen, which initially triggers the aggregation of platelets. 

Prothrombin normally contains 10 y-carboxyglutamate residues in the amino terminal region. In the presence of high concentrations of warfarin, a completely uncarboxylated precursor, preprothrombin, is released into the circulation. Before the nature of this precursor protein was known, it was called protein induced by vitamin K absence or antagonism (PIVKA), a term that is sometimes still used. 

Thrombin, which catalyzes the proteolysis of fibrinogen, circulates as an inactive precursor, prothrombin, which in turn is activated by partial proteolysis to remove a peptide sequence that masks the catalytic site. There are two distinct pathways leading to the activation of prothrombin to thrombin (see Figure 5.3) ... 

Diagnostic importance is also attributed to des-y-car-boxy prothrombin (60-80% positivity in HCC) (H.A. Liebman et af, 1984). (90, 120, 133, 154) It is synthesized in the normal hepatocytes and therefore also in HCC. The diagnostic accuracy in small hepatocellular carcinomas (< 3 cm) could be greatly improved by determining this precursor prothrombin (PIVKAII) in combination with AFP. A decrease in the factor-II index, i.e. (factor VII + factor X) - (factor II) = >15, has proved to be a specific and independent marker of HCC. In addition, isoferritins, Regan-AP, telomerase activity (99) and L-fucosidase as well as CEA variants may be helpful in the demarcation of HCC. Laboratory diagnosis of HCC is indeed much more reliable if various important parameters are added, (s. tab. 37.6)... 

Vitamin K is involved in the activation of precursors of prothrombin and other clotting factors by carboxylation of glutamate residues. 

---