HUMAN SERUM PARAOXONASE/ARYLESTERASE

人类血清对氧磷酶/芳香酯酶具有药物遗传学意义，因为 它催化芳香族羧酸酯和芳香族羧酸酯的水解。 有机磷酸盐，如DPF(二异丙基氟磷酸盐)，对氧磷， 梭曼，沙林，可能还有一些氨基甲酸酯。两个基因决定的 血清酯酶的多态形式，我们称之为A型和B型， 特别是在对氧磷酶活性上的差异；B-型是 对氧磷酶活性是A型的几倍。 我们已经克隆了决定这种酶结构的基因，并计划 鉴定两种多态形式的DNA结构基础 酯酶。我们将寻找酯酶的其他变异形式 用血细胞DNA和聚合酶链式反应(PCR)检测 来自血清芳香酯酶不同的人的编码DNA序列 在数量上或在性质上来自共同的A和B 等位酶形式。还将寻找具有遗传基因的个人 确诊为完全性酯酶缺乏症，即完全缺乏 芳香酯酶的活性，以帮助确定这种酯酶可能具有的功能 有正常的新陈代谢，以及它的生理底物可能是什么。 纯化的酯酶将被更详细地鉴定，特别是 其活性中心氨基酸组成、物理性质、底物 特异性，以及它与其他酯酶的结构同源性 半胱氨酸在它们的活性中心。它与高密度脂蛋白的密切联系- 还将对血清中的复合体进行评估。

Human serum paraoxonase/arylesterase is of pharmacogenetic interest because it catalyzes the hydrolysis of both aromatic carboxylic acid esters and organophosphates, such as DPF (diisopropylfluorophosphate), paraoxon, soman, sarin, and presumably, some carbamates. Two genetically determined polymorphic forms of the serum esterase, which we call types A and B, differ particularly in their paraoxonase activities; the B-type being several-fold times more effective than the A-type in paraoxonase activity. We have cloned the gene determining the structure of this enzyme and plan to identify the DNA structural basis of the two polymorphic forms of the esterase. We will search for additional variant forms of the esterase using blood cellular DNA and the polymerase chain reaction (PCR) to examine the coding DNA sequence from people with serum arylesterases that differ quantitatively or in qualitative properties from the common A and B allozymic forms. Individuals will also be sought who have a genetically determined complete esterase deficiency, i.e., who have a total lack of any arylesterase activity, to help determine what functions this esterase may have in normal metabolism and what its physiological substrates might be. The purified esterase will be characterized in further detail, particularly its active center amino acid components, physical properties, substrate specificity, and its structural homology with other esterases having cysteine in their active centers. Its close association with the HDL- complex in serum will also be evaluated.