PATHOBIOLOGY OF HUMAN FACTOR IX: STRUCTURE AND FUNCTION

因子IX蛋白，虽然在血浆中的浓度很低， 对止血来说是必不可少的。先天性因子缺乏症患者 血友病B，有出血性疾病，患病率为5% 10万只雄性。这些病人需要过多的献血。 产品来控制他们的出血，从而过上几乎正常的生活。 获得性因子IX缺陷本身并不常见，但伴随着 肝病中其他维生素K依赖凝血因子的抑制 以及服用口服抗凝剂的患者。手术中出血的处理 后天缺陷要困难得多。 为了发挥凝血功能，必须将因子IX转化为活性因子 形态，因子IXa。这种情况是如何发生的，无论是正常的还是病理的 人们对限制其活动的手段知之甚少。自.以来 凝血因子IX的激活是一系列 导致凝血的生化反应，它提供了极好的 引发或控制非常常见的疾病的可能性 血栓形成的可能性。更好地理解这种等离子体之间的相互作用 蛋白质、血小板(凝血细胞)和血管内壁 需要血管。 提出了阐明功能异常和结构异常的建议 血友病(异常)因子IX蛋白的碱基将提供见解 这种凝血蛋白在正常的血液凝结和 血栓形成。抗体技术纯化异常凝血因子IX蛋白的研究 病人的血浆正在研发中。异常的凝血因子IX蛋白 会被标记上微量的放射性物质，并由Sensitive研究 免疫化学方法。鉴定将包括微筛查 测试：1)它们从不活跃的前体转化为 活性形式，2)它们被某些酶分解的能力，3) 它们作为酶的功能特性以及4)它们与 辅因。我们还将能够评估不稳定的变体，这些变体 比正常情况下从血液循环中清除得更快。的研究 血友病因子IX基因将被用来确定 通过鉴定特定的血友病因子IX蛋白的结构 遗传密码中的异常。

Factor IX protein, although present in a very low concentration in plasma, is essential for hemostasis. Patients with congenital deficiency of factor IX, hemophilia B, have a bleeding disorder with a prevalence of 5 per 100,000 males. These patients require an inordinate supply of donor blood products to control their bleeding and thus lead nearly normal lives. Acquired factor IX defects are uncommon by themselves but accompany the depression of other vitamin K-dependent clotting factors in liver disease and in patients on oral anticoagulants. Management of bleeding in the acquired defects is much more difficult. In order to function in clotting, factor IX must be converted to an active form, factor IXa. Just how this occurs either normally or pathologically is poorly understood as are the means of limiting its activity. Since factor IX activation is one of the initial steps of a long series of biochemical reactions which lead to clotting, it provides excellent potential for either setting off or controlling the very common disorders of thrombosis. A greater understanding of interactions between this plasma protein, blood platelets (the clotting cells) and the innner walls of the blood vessels is needed. It is proposed that elucidating the functional abnormalities and structural bases of hemophilic (abnormal) factor IX proteins will provide insights into the role of this clotting protein in normal blood clotting and thrombosis. Antibody techniques to purify abnormal factor IX proteins from patients' plasmas are being developed. The abnormal factor IX proteins will be labeled with a trace of radioactivity and studied by sensitive immunochemical methods. Characterization will include micro-screening tests for: 1) their ability to be converted from an inactive precursor to the active form, 2) their ability to be broken down by certain enzymes, 3) their functional properties as enzymes and 4) their interactions with cofactors. We will also be able to assess for unstable variants which are cleared more rapidly than normal from the circulation. Studies of hemophilic factor IX genes will be used to determine what is wrong with the structure of a given hemophilic factor IX protein by identifying the abnormality in the genetic code.