Urokinase

Urokinase, also known as urokinase-type plasminogen activator (uPA), is a serine protease enzyme that plays a crucial role in the breakdown of blood clots. It is naturally present in humans and other animals, and it is involved in various physiological processes, including thrombolysis and extracellular matrix degradation .

The human urokinase protein was first discovered by McFarlane and Pilling in 1947 . Initially isolated from human urine, urokinase is also found in the blood and the extracellular matrix of many tissues . The enzyme was granted FDA approval on January 16, 1978 .

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 (zymogen) of the serine protease plasmin. Activation of plasmin triggers a proteolytic cascade that participates in thrombolysis or extracellular matrix degradation, depending on the physiological environment .

Urokinase activates plasminogen to an active fibrinolytic protease called plasmin. This activation occurs through specific cleavage of an Arg-Val bond in plasminogen . The enzyme remains connected between its two chains by a sulfhydryl bond . Urokinase’s action is short-lived due to its short half-life, and patients should be aware of potential risks such as bleeding, anaphylaxis, infusion reactions, and cholesterol embolization .

In clinical settings, urokinase is used for the treatment of various thromboembolic conditions. These include:

• Acute massive pulmonary embolism
• Acute thrombi obstructing coronary arteries
• Occlusive thromboemboli in peripheral arteries and grafts
• Restoration of patency to intravenous catheters

Recombinant urokinase is produced using biotechnological methods to ensure a consistent and pure product. This form of urokinase has been on the market for over thirty years in Europe and Asia, used in various human medicines for clot lysis in conditions such as peripheral arterial occlusion, deep venous thrombosis, stroke, catheter clearance, and myocardial infarction .

The PLAU gene encodes urokinase in humans, standing for "plasminogen activator, urokinase" . This gene is involved in the degradation of the extracellular matrix and possibly tumor cell migration and proliferation. A specific polymorphism in this gene may be associated with late-onset Alzheimer’s disease and decreased affinity for fibrin-binding .