Урокиназа

Описание

Urokinase is an enzyme that is extracted from human urine or kidney cells, which directly cleaves specific peptide bonds, in particular the Arg-560–Val-561 bond in the plasminogen molecule, thus transforming it into plasmin.

Химические свойства

White or almost white, amorphous powder.

Использование

The effect of systemic administration of urokinase is unclear. One study reported the effectiveness of superselective ophthalmic artery fibrinolytic therapy of urokinase for CRVO. Urokinase was infused through a microcatheter into the ostium of the ophthalmic artery via the femoral artery. Six eyes of 26 patients had a significant improvement in VA 24 hours after the fibrinolysis; eyes with combined central retinal artery occlusion and CRVO with recent visual impairment appeared to be the most responsive.

Общее описание

Urokinase (Abbokinase) is a glycosylatedserine protease consisting of 411 amino acid residues,which exists as two polypeptide chains connected by a singledisulfide bond. It is isolated from human urine or tissueculture of human kidneys. The only known substrate ofurokinase is plasminogen, which is activated to plasmin, afibrinolytic enzyme. Unlike streptokinase, urokinase is adirect activator of plasminogen. Urokinase is nonantigenicbecause it is an endogenous enzyme and, therefore, may beused when streptokinase use is impossible because of antibodyformation. It is administered intravenously or by theintracoronary route. Its indications are similar to those ofstreptokinase.

Механизм действия

Urokinase is an enzyme with the ability to directly degrade fibrin and fibrinogen. It is now isolated from cultures of human fetal kidney cells and is composed of two polypeptide chains with molecular weights of 32 and 54 kDa.

Фармакокине?тика

This method of isolation is much more efficient than the original isolation of urokinase from human urine. Because of its source, the human body does not see urokinase as a foreign protein. Therefore, it lacks the antigenicity associated with streptokinase and frequently is used for patients with a known hypersensitivity to streptokinase. Plasmin cannot be used directly because of the presence of naturally occurring plasmin antagonists in plasma. No such inhibitors of urokinase exist in the plasma, however, allowing this enzyme to have clinical utility. Even so, urokinase is much more expensive (threefold the price of streptokinase) and has an even shorter half-life (15 minutes). Urokinase also has other fibrin-nonspecific actions similar to streptokinase.

Профиль безопасности

An experimental teratogen. Experimental reproductive effects. Used in the treatment of diseases caused by blood clots.

Методы очистки

Crystallisation of this enzyme is induced at pH 5.0 to 5.3 (4o) by careful addition of NaCl with gentle stirring until the solution becomes turbid (silky sheen). The NaCl concentration is increased gradually (over several days) until 98% of saturation is achieved whereby urokinase crystallises out as colourless thin brittle plates. It can be similarly recrystallised to maximum specific activity [104K CTA units/mg of protein (Sherry et al. J Lab Clin Med 64 145 1964)]. [Lesuk et al. Science 147 880 1965, NMR: Bogusky et al. Biochemistry 28 6728 1989.] Itisa plasminogen activator [Gold et al. Biochem J 262 1989, de Bock & Wang Med Res Rev 24(1) 13 2004].