Prothrombin carbohydrate

Prothrombin is the precursor of the serine protease thrombin, essential for normal haemostasis in activation of platelets and in catalysing the polymerisation of fibrinogen to fibrin. It is synthesized in the liver and contains about 8% total carbohydrate in four N-glycans. Three of these lie on the Pro region and only one is present on the mature a-thrombin molecule. The structure of the thrombin glycan has been determined by mass spectrometry and is the same as that shown in Fig. 5 A with fucose absent or present [77]. 

The primary functions of albumin are to help maintain the osmotic (oncotic) transmural pressure differential that ensures proper mass exchange between blood and interstitial fluid at the capillary level and to serve as a transport carrier molecule for several hormones and other small biochemical constituents (such as some metal ions). The primary function of the globulin class of proteins is to act as transport carrier molecules (mostly of the a and p class) for large biochemical substances, such as fats (lipoproteins) and certain carbohydrates (muco- and glycoproteins) and heavy metals (mineraloproteins), and to work together with leukocytes in the body s immune system. The latter function is primarily the responsibflity of the y class of immunoglobulins, which have antibody activity. The primary function of fibrinogen is to work with thrombocytes in the formation of a blood clot — a process also aided by one of the most abundant of the lesser proteins, prothrombin (MW 62,000). 

Thrombin a blood coagulation enzyme, responsible for the conversion of fibrinogen to fibrin. T. is a glycoprotein (5% carbohydrate), M, 39,000, produced by activation of Prothrombin (see). It is a typical Serine protease (see) with catalytically important residues Hissg, Aspjgj and Sett, in the B-clu, and considerable sequence homology with trypsin, chy-motiypsin and elastase. Autolysis of T, leading to a decrease of M, from 39,000 to 26,000 at the expense of the B-chain M, 33,000 to 19 00) causes no loss of activity. 

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]. 

The previously-stated existence of four carbohydrate chains in dog prothrombin has been challenged. Although four glycopeptides have been isolated by use of a combination of gel filtration and ion-exchange chromatography, it is proposed that the differences are due to microheterogeneity of the glycoprotein. 

The carbohydrate sequence of some coagulation factors has been determined (prothrombin or F II, thromboplastin or F X, fibrinogen or F I, and the fibrinolytic serine protease, plasmin), but only a few investigations have been reported on the functional significance of the carbohydrate residues (Mizuochi et al 1979, Mizuochi et al 1980, Gati and Straub 1978, Hayes and Castellino 1979, Lijinen et al 1981). 

Desialylation destroys the protease activity of plasminogen. Functional prothrombin arises from its precursor by two post-translational modifications a vitamin K-dependent carboxylation of glutamic acid residues, followed by glycosylation in the carboxylated region (prothrombin fragment 1 AS 1-156). Deglycosylation of prothrombin in the presence of Ca " leads to greatly increased self-association this occurs at certain contact points on the molecule, which are probably concealed by carbohydrate chains in the intact molecule (Fletcher et al... 

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