plazminogen

Plasminogen, sometimes spelled plazminogen, is the zymogen of plasmin, a serine protease that mediates fibrinolysis. It is produced primarily by the liver and circulates in the blood as a single-chain glycoprotein of about 92 kDa.

Molecular structure and activation: Plasminogen consists of an N-terminal domain with five kringle repeats and a C-terminal serine protease domain. It binds to fibrin and cell surfaces via lysine-binding sites in the kringle domains. Activation by plasminogen activators cleaves at the Arg561-Val562 bond to form plasmin, a two-chain enzyme comprised of heavy and light chains and housing the catalytic triad necessary for proteolysis.

Activation and function: Tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) convert plasminogen to plasmin. Plasmin degrades fibrin clots and various extracellular matrix proteins, contributing to clot dissolution and tissue remodeling. It can also activate other proteases and influence wound healing. Plasmin activity is regulated by inhibitors such as alpha-2 antiplasmin and plasminogen activator inhibitors (PAI-1, PAI-2) to prevent excessive proteolysis.

Clinical relevance: Hereditary plasminogen deficiency is associated with ligneous conjunctivitis and other mucosal lesions due to impaired fibrinolysis. Plasminogen levels and activity can be measured in clinical assays. Management of deficiency or related disorders is specialized and may involve replacement therapy in some cases.

Genetics: The PLG gene encodes plasminogen and is located on chromosome 6 (6q26-27). The protein functions in physiological fibrinolysis and tissue remodeling, with dysregulation implicated in thrombotic risk, cancer invasion, and inflammatory processes.