ATP-LINKED EFFECTORS OF NA,K-ATPASE AND CATARACT

在某些老年性白内障中，晶状体混浊伴有异常。 透镜状Na+和/或K+浓度。这些反常的单价阳离子 浓度可能是也可能不是由血浆故障引起的 膜结合Na，K-ATPase。Na，K-ATPase含有多种必需氨基酸 侧链的修改可能会导致故障，而 Na，K-ATPase的酶功能，近饱和水平的水解性 将保持不变。已经证明，过氧化氢 器官培养牛晶状体Na，K-ATPase的本质修饰 抑制K+的运输，同时使水解物接近饱和 三磷酸腺苷水平基本正常。然而，Na，K-ATPase的氧化不是 改变泵功能的唯一途径。这种酶是已知的 具有某些氨基官能团(玻尔基)，其滴定在 生理范围控制酶的构象状态。 Na+和K+的转运与Na+和K+的相互转化密切相关 介于两种构象状态之间的酶。因此，修改 其中的玻尔群可能会显著改变交通 Na，K-ATPase的功能。由于玻尔基团的pH值范围 Na，K-ATPase滴定物类似于Alpha和 血红蛋白的β链，体内翻译后糖基化， 氨基甲酰化或烷基化可能发生在疾病状态，如 失控的糖尿病、尿毒症或药物治疗。为此，体外培养 Na，K-ATPase的玻尔胺与葡萄糖、氰酸盐和 烷基化试剂的选择及酶的表征 功能应该产生关于体内可能存在的 用类似的试剂对酶进行修饰。

In certain senile cataracts, lens opacification is accompanied by abnormal lenticular Na+ and/or K+ concentrations. These abnormal monovalent cation concentrations may or may not result from malfunction of the plasma membrane bound Na,K-ATPase. The Na,K-ATPase has many essential amino acid side chains whose modifications could lead to malfunction while the enzymatic function of Na,K-ATPase, the hydrolysis of near-saturating levels of ATP, would remain unchanged. It has already been demonstrated that H2O2 modification of Na,K-ATPase in the organ cultured bovine lens essentially inhibits K+ transport while leaving the hydrolysis of near saturating levels of ATP essentially normal. However, oxidation of Na,K-ATPase is not the only route by which pump function can be altered. The enzyme is known to have certain amino functional groups (Bohr groups) whose titration in the physiological range control the conformational state of the enzyme. The transport of Na+ and K+ is linked intimately to the interconversion of the enzyme between its two conformational states. Therefore, modification of these Bohr groups might be expected to significantly alter the transport function of Na,K-ATPase. Since the pH range in which the Bohr groups of Na,K-ATPase titrate is similar to the NH2 terminal groups of the Alpha and Beta chains of hemoglobin, in vivo post-translational glycosylation, carbamylation or alkylation might occur in disease states such as uncontrolled diabetes, uremia or drug therapy. To this end, the in vitro reaction of the Bohr amines of Na,K-ATPase with glucose, cyanate and selected alkylating agents followed by characterization of enzymatic function should yield valuable information regarding the possible in vivo modification of the enzyme with similar agents.