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

在某些老年性白内障中，透镜混浊伴有异常的 晶状体Na+和/或K+浓度。 这些不正常的一价阳离子 浓度可能或可能不是由等离子体的故障引起的 膜结合Na，K-ATPase。 Na，K-ATPase含有多种必需氨基酸 侧链，其修饰可能导致故障，而 Na，K-ATPase的酶功能，水解接近饱和水平 ATP保持不变。 已经证明，H2 O2 培养牛透镜Na，K-ATP酶的修饰 抑制K+转运，同时使水解接近饱和 ATP水平基本正常。 然而，Na，K-ATP酶的氧化不是 这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（玻尔基团），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。 酶的两种构象状态。 因此，修改 这些玻尔集团的预期可能会显着改变运输 Na，K-ATP酶的功能。 由于pH值范围内，玻尔集团的 Na，K-ATP酶滴定类似于α和β-ATP酶的NH 2末端基团。 血红蛋白的β链，体内翻译后糖基化， 氨甲酰化或烷基化可能发生在疾病状态， 未控制的糖尿病、尿毒症或药物治疗。 为此，体外 Na，K-ATPase的Bohr胺与葡萄糖、氰酸酯和 选择的烷化剂，然后表征酶促 功能应该产生有价值的信息，关于可能在体内 用类似试剂修饰酶。

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.