Plasminogen

Plasminogen is a precursor of the potent fibrin-degrading serine proteinase, plasmin. It is a single human plasminogen peptide chain consisting of 791 amino acid residues and two carbohydrates attached at the Asn-289 and Thr-346. With the presence of disulfide bonds, plasminogen's structure is divided into a contiguous series of five homologous regions called kringles, so-called because of their resemblance to the Danish Kringle - a danish pastry.

Human plasminogen consists of an amino-terminal peptide, five kringle modules and a protease domain. Plasminogen is converted to plasmin by cleavage of Lys-77 releasing the N-terminal peptide. Activator proteins cleavage of the peptide bond at Arg-561 then follows. A two chain molecule is formed in which the heavy chain containing the five modules remains linked to the light chain where the catalytic domain is found through 2 disulfide bonds.

Each kringle module is comprised of about 78 residues which are very homologous in sequence. Kringles are also present in a number of blood coagulation proteins and serine proteases including prothrombin, tissue-type plasminogen activators, urokinase plasminogen activator, Factor X and tissue factor pathway inhibitor. In addition, these modules can also be found in hepatocyte growth factors which are implicated in increased motility of various epithelial and endothelial cells and the proliferation of primary hepatocytes. The presence of kringles in these different proteins suggest that these enzymes might share a common primitive ancestor during evolution.

Plasminogen is normally converted to plasmin by the action of plasminogen activotor inhibitors - either tissue plasminogen activator (tPA) or urokinase type plasminogen activator (uPA).

In the Hemostasis and Thrombosis Laboratory, plasminogen activity in plasma is measured in a chromogenic assay. Plasminogen is converted to plasmin by tPA and the generated plasmin measured with a specific chromogenic substrate. The normal range is 70 - 130%.

Decreased plasminogen levels may represent an increased risk of thrombosis. Rarely, individuals may have a defective plasminogen molecule (dysplasminogenemia).