Fungal proteases and the mammalian kinin system: I. Brinolase-catalyzed kinin formation and S2160 hydrolysis.
Brinolase, a fungal protease advocated for thrombolytic therapy, released kinin peptides from semi-purified kininogens of the human, rabbit, guinea pig, and mouse, and moreover cleaved an arginyl bond of the chromogenic peptide S2160. Its kinetics demonstrated marked differences from the mammalian protease trypsin. Whereas trypsin liberated 100% of the available kinin in 30 min at pH 8, brinolase generated a maximum of only 22% under optimal conditions, viz. incubation of 5 microgram/ml enzyme at pH 4.7 for 5 min. Longer incubations yielded less detectable kinin. This maximal release at acidic pH was not due to increased kininogen consumption, nor was it inhibited by the acid protease inhibitor pepstatin. Evidence is presented that brinolase, unlike trypsin, might both release and destroy kinins.
Fungal proteases and the mammalian kinin system: I. Brinolase-catalyzed kinin formation and S2160 hydrolysis. Brinolase, a fungal protease advocated for thrombolytic therapy, released kinin peptides from semi-purified kininogens of the human, rabbit, guinea pig, and mouse, and moreover cleaved an arginyl bond of the chromogenic peptide S2160. Its kinetics demonstrated marked differences from the mammalian protease trypsin. Whereas trypsin liberated 100% of the available kinin in 30 min at pH 8, brinolase generated a maximum of only 22% under optimal conditions, viz. incubation of 5 microgram/ml enzyme at pH 4.7 for 5 min. Longer incubations yielded less detectable kinin. This maximal release at acidic pH was not due to increased kininogen consumption, nor was it inhibited by the acid protease inhibitor pepstatin. Evidence is presented that brinolase, unlike trypsin, might both release and destroy kinins.