Zymogens and cofactors of blood coagulation.

Zymogens and cofactors of blood coagulation.
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DOI:
10.3109/10409238009105472
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发表时间:
1980
期刊:
CRC critical reviews in biochemistry
影响因子:
--
通讯作者:
Yale Nemerson;B. Furie
Yale Nemerson;B. Furie
中科院分区:
其他
文献类型:
--
作者:
Yale Nemerson;B. Furie

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血液凝固是一系列丝氨酸蛋白酶的酶原被顺序激活的系统。在这方面,凝血和同源胰腺酶原的激活之间几乎没有根本区别。然而,有几个方面独特的混凝,详细讨论。它们是(1)最佳反应速率对高分子量蛋白质或脂蛋白辅因子的要求,(2)进一步区分该系统的膜或膜样表面的要求;(3)大多数反应需要金属离子(与胰腺丝氨酸蛋白酶相反)与四种维生素K-γ-羧基谷氨酸中新描述的氨基酸γ-羧基谷氨酸的含量有关。依赖性蛋白质,关于凝血酶原上的金属结合位点的最新数据进行了详细讨论;和(4)的独特性相比,那些激活胰腺酶原的起始反应,只要没有相应的酶肠激酶已被确定。这一现象的影响进行了分析,特别注意某些酶原的内源性活性在启动凝血的潜在作用。文章最后处理的具体问题,伴随着分析一个系统,其中许多丝氨酸蛋白酶缺乏绝对的特异性产生和调节。
Blood coagulation is a system in which a series of zymogens of serine proteases are sequentially activated. In this regard, there is little fundamental difference between coagulation and the activation of the homologous pancreatic zymogens. There are, however, several aspects unique to coagulation which are discussed in detail. These are (1) the requirement for a high-molecular-weight protein or lipoprotein cofactor for optimal reaction rates, (2) the requirement for membranes or a membrane-like surface which further distinguishes this system; (3) a metal ion requirement for most reactions (in contrast to the pancreatic serine proteases) relating to the content of the newly described amino acid gamma-carboxyglutamic acid in the four vitamin K-dependent proteins, regarding which recent data relating to the metal binding sites on prothrombin are discussed in detail; and (4) the uniqueness of the initiating reactions in comparison to those which activate the pancreatic zymogens, insofar as no enzyme corresponding to enterokinase has been identified. The implications of this phenomenon are analyzed with particular attention to the potential role of the endogenous activity of certain zymogens in initiating coagulation. The article deals finally with the specific problems attendant on analyzing a system in which many serine proteases lacking absolute specificity are generated and regulated.