MEMBRANOUS COPPER AMINE OXIDASE

铜胺氧化酶(CAO)是一类能将内源胺转化为氨、过氧化氢和醛的酶。到目前为止，在血清结合和膜结合两种类型的CAO中，膜型CAO还没有得到深入的研究。我们打算获得膜CAO基因的克隆，以便在哺乳动物细胞中表达该酶，并对其动力学性质、辅因子形成和催化机制进行研究。鉴于CAO在几种疾病中具有潜在的重要作用，我们打算通过组合方法合成基于肼的抑制剂。我们希望，对这些化合物的筛选将产生一种膜结合的CAO的特异性抑制剂。我们还打算研究膜CAO作为质膜H_2O_2生成器的可能作用。这种缓慢的、原位产生的过氧化氢可能会充当信号媒介，从而影响负责细胞死亡、细胞增殖和炎症的基因。

DESCRIPTION Copper amine oxidases (CAOs) are a family of enzymes that convert endogenous amines to ammonia, hydrogen peroxide and aldehydes. To date, of t5he two types of CAOs, serum and membrane bound, the membranous CAOs have not been thoroughly studied. We intend to obtain the previously isolated clone for membranous CAO cDNA in order to express the enzyme in mammalian cells and characterize its kinetic properties, cofactor formation and catalytic mechanism. Given that CAOs are potential important in several diseases, we intend to synthesize hydrazine-based inhibitors by combinatorial methods. It is our hope that screening of these compounds will yield an inhibitor specific for membrane bound CAOs. We also intend to investigate the possible role of membranous CAO as a generator of H2O2 at the plasma membrane. It is possible that the slow, in situ generation of peroxide will act as a signaling agent, thereby influencing the genes responsible for cell death, cell proliferation and inflammation.