Plasminogeenin

Plasminogeenin, also known as plasminogen, is the zymogen of the serine protease plasmin. It is produced mainly by the liver and circulates in blood as a 92-kilodalton glycoprotein that becomes active when converted to plasmin. Structurally, plasminogen contains an N-terminal activation peptide, five kringle domains that mediate interactions with fibrin and cell surfaces, and a C-terminal serine protease domain that is unleashed upon activation.

Activation and function: Plasminogen is activated to plasmin by tissue-type plasminogen activator (tPA) or urokinase-type plasminogen activator (uPA). Plasmin is a broad-spectrum protease that cleaves fibrin to dissolve clots and can also degrade other extracellular matrix components. By binding to fibrin via its kringle domains, plasminogen localizes proteolysis to sites of vascular injury, promoting targeted fibrinolysis while limiting systemic proteolysis.

Regulation: Plasmin activity is tightly controlled by inhibitors, chiefly alpha-2-antiplasmin, and by plasminogen activator inhibitors (PAI-1 and PAI-2) that regulate the generation of plasmin. Lysine analogs, such as tranexamic acid and aminocaproic acid, can inhibit plasminogen binding to fibrin and are used clinically to reduce bleeding.

Clinical relevance: Deficiency of plasminogen can lead to Ligneous conjunctivitis and other mucosal lesions due to impaired fibrinolysis. Abnormal plasminogen activation is implicated in bleeding disorders, thrombosis, and cancer invasion through effects on extracellular matrix remodeling. Diagnostic assessment includes measuring plasminogen antigen or activity, while therapies may involve plasminogen activators or antifibrinolytics depending on the clinical context.