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Inhibition of Serine Proteases of the Blood Coagulation System by Squash Family Protease Inhibitors

1994; Oxford University Press; Volume: 116; Issue: 5 Linguagem: Inglês

10.1093/oxfordjournals.jbchem.a124621

1756-2651

Kaeko Hayashi, Tohru Takehisa, Nobuaki Hamato, Ryo Takano, Saburo Hara, Toshiyuki Miyata, Hisao Kato,

Protease and Inhibitor Mechanisms

Squash family inhibitors are the smallest protein serine protease inhibitors, being composed of approximately 30 amino acid residues. We isolated 8 squash family inhibitors from the seeds of bitter gourd, squash, gourd and luffa and examined their effect on serine proteases of the blood coagulation system. Five of them prolonged the activated partial thromboplastin time of human plasma to various extents, but three did not. Only Momordica charantia (bitter gourd) trypsin inhibitor-II prolonged the prothrombin time of human plasma. All inhibitors inhibited the amidolytic activities of factor XIIa, plasma kallikrein, factor Xa, but did not inhibit significantly those of factor XIa, factor IXa, factor VIIa, and thrombin. Ki values for factor XIIa, plasma kallikrein, and factor Xa were in the order of 10(-6)-10(-9), 10(-4)-10(-5), and 10(-4)-10(-6)M, respectively. The prolongation of the activated partial thromboplastin time by inhibitors appeared to correspond to their inhibitory potencies for factor XIIa. Momordica charantia trypsin inhibitor-II, which has the strongest inhibitory potency toward the amidolytic activity of factor Xa, with a Ki value 10-100 times smaller than those of other inhibitors, inhibited the activation of factor X by factor VIIa-tissue factor complex or factor IXa, while others did not.