Nobar Shila M, Guy-Crotte Odette, Rabaud Michel, Bieth Joseph G
Laboratoire d'Enzymologie, INSERM U392, Université Louis Pasteur de Strasbourg, F-67400 Illkirch, France.
Biol Chem. 2004 May;385(5):423-7. doi: 10.1515/BC.2004.048.
Human plasma alpha1-antitrypsin inhibits human pancreatic trypsin, chymotrypsin and elastase, which are massively released into the blood stream during acute pancreatitis. To examine whether the plasma proteins of individuals with genetic deficiency of alpha1-antitrypsin are protected against the deleterious action of these enzymes by other inhibitors, we have tested their inhibition by alpha2-antiplasmin and antithrombin. We have determined the inhibition rate constants kass and calculated d(t), the in vivo inhibition time. Surprisingly, trypsin is inhibited faster by alpha2-antiplasmin [kass=2.5 x 10(6) M(-1)S(-1), d(t)=2.3 s] and antithrombin [kass=1.7 x 10(5) M(-1)s(-1), d(t)=5.8 s] than by alpha1-antitrypsin [d(t)=17 s or 116 s in alpha1-antitrypsin-sufficient or alpha1-antitrypsin-deficient individuals, respectively]. Low molecular weight heparin accelerates the inhibition of trypsin by antithrombin by a factor of 16 [d(t)=0.36 s]. Antithrombin and alpha2-antiplasmin are not physiological inhibitors of chymotrypsin and elastase. These enzymes are, however, physiologically inhibited by alpha1-antitrypsin and alpha1-antichymotrypsin even in alpha1-antitrypsin-deficient individuals. We conclude that (i) low molecular weight heparin may be helpful in the management of acute pancreatitis, and (ii) genetically determined alpha1-antitrypsin deficiency probably does not lead to a significantly increased risk of plasma protein degradation during this disease.
人血浆α1-抗胰蛋白酶可抑制人胰腺中的胰蛋白酶、糜蛋白酶和弹性蛋白酶，在急性胰腺炎期间这些酶会大量释放入血流。为了研究α1-抗胰蛋白酶基因缺陷个体的血浆蛋白是否受到其他抑制剂的保护而免受这些酶的有害作用，我们检测了α2-抗纤溶酶和抗凝血酶对它们的抑制作用。我们测定了抑制速率常数kass，并计算了体内抑制时间d(t)。令人惊讶的是，α2-抗纤溶酶[kass = 2.5×10(6) M(-1)S(-1)，d(t) = 2.3 s]和抗凝血酶[kass = 1.7×10(5) M(-1)s(-1)，d(t) = 5.8 s]对胰蛋白酶的抑制速度比α1-抗胰蛋白酶更快[在α1-抗胰蛋白酶充足或α1-抗胰蛋白酶缺陷个体中，d(t)分别为17 s或116 s]。低分子量肝素可使抗凝血酶对胰蛋白酶的抑制作用加快16倍[d(t) = 0.36 s]。抗凝血酶和α2-抗纤溶酶不是糜蛋白酶和弹性蛋白酶的生理性抑制剂。然而，即使在α1-抗胰蛋白酶缺陷个体中，这些酶也受到α1-抗胰蛋白酶和α1-抗糜蛋白酶的生理性抑制。我们得出结论：(i)低分子量肝素可能有助于急性胰腺炎的治疗，(ii)基因决定的α1-抗胰蛋白酶缺乏在这种疾病中可能不会导致血浆蛋白降解风险显著增加。
