Urokinase Human

Urokinase was first discovered by McFarlane and Pilling in 1947, although it was not named at that time . It was originally isolated from human urine, which is reflected in its name. Besides urine, urokinase is also present in the blood and the extracellular matrix of various tissues .

Urokinase is a 411-residue protein consisting of three domains: the serine protease domain, the kringle domain, and the EGF-like domain . The primary physiological substrate of urokinase is plasminogen, an inactive form of the enzyme plasmin. Urokinase converts plasminogen to plasmin by cleaving a specific peptide bond. Plasmin then participates in a proteolytic cascade that leads to the degradation of fibrin, a key component of blood clots .

The gene encoding urokinase in humans is known as PLAU (plasminogen activator, urokinase) . This gene is located on chromosome 10 and is expressed in various tissues. The protein exists in two forms: high molecular weight urokinase (HMW-uPA) and low molecular weight urokinase (LMW-uPA). HMW-uPA can be further processed into LMW-uPA, which is proteolytically active but does not bind to the urokinase receptor .

Urokinase is used clinically as a thrombolytic agent to dissolve blood clots in patients with conditions such as pulmonary embolism, myocardial infarction, and deep vein thrombosis . It is administered intravenously and works by converting plasminogen to plasmin, which then breaks down fibrin in blood clots .

Beyond its role in fibrinolysis, urokinase is involved in various biological processes including embryogenesis, cell migration, tissue remodeling, ovulation, and wound healing . It is also detected in many cancers and is thought to play a role in tumor cell migration and proliferation .

While urokinase is effective in dissolving blood clots, it carries a risk of severe bleeding, which can be life-threatening . Patients receiving urokinase should be closely monitored for signs of bleeding, and the drug should be used with caution in individuals with conditions that predispose them to bleeding .