The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain.
The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain.
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DOI：
10.1016/s0021-9258(19)70391-3
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发表时间：
1980-11
期刊：
影响因子：
--
通讯作者：
Loretta M. HallcherS;W. Sherman
中科院分区：
文献类型：
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作者：
Loretta M. HallcherS;W. Sherman
从牛脑中部分纯化了肌醇-1-磷酸酶。该酶的分子量约为58，000。L-肌醇1-磷酸和D-肌醇1-磷酸都被该酶水解，（-）-手性肌醇3-磷酸和2 '-AMP也被水解。三磷酸肌醇不是底物。磷酸酶是完全依赖于Mg 2+，其具有1 mM的Km。钙和锰离子是Mg 2+结合的竞争性抑制剂，Ki值分别为18 μ M和2 μ M。氯化锂抑制水解的L-和D-肌肌醇1-磷酸的程度为50%，在0.8 mM的浓度。从睾丸的磷酸酶类似地抑制锂。锂离子是Mg 2+结合的非竞争性抑制剂和肌醇1-磷酸结合的非竞争性抑制剂。由于氯化锂给药引起大鼠脑中肌醇1-磷酸水平升高和肌醇水平降低（Allison，1978），并且由于这些作用被抗胆碱能药物阻断，因此我们检查了胆碱能激动剂和拮抗剂对酶的影响，但未发现任何影响。讨论了锂离子对该酶的抑制与锂的药理作用有关的可能性。
myo-Inositol-1-phosphatase has been partially purified from bovine brain. The enzyme has a molecular weight of about 58,000. Both L-myo-inositol 1-phosphate and D-myo-inositol 1-phosphate are hydrolyzed by the enzyme as well as (-)-chiro-inositol 3-phosphate and 2'-AMP. Triphosphoinositide is not a substrate. The phosphatase is completely dependent on Mg2+, which has a Km of 1 mM. Calcium and manganese ions are competitive inhibitors of Mg2+ binding with Ki values of 18 microM and 2 microM, respectively. Lithium chloride inhibits the hydrolysis of both L- and D-myo-inositol 1-phosphate to the extent of 50% at a concentration of 0.8 mM. The phosphatase from testis is similarly inhibited by lithium. Lithium ion is a noncompetitive inhibitor of Mg2+ binding and an uncompetitive inhibitor of myo-inositol 1-phosphate binding. Because lithium chloride administration elicits both an increase in the levels of myo-inositol 1-phosphate and a decrease in the levels of myo-inositol in rat brain (Allison, 1978), and because these actions are blocked by anticholinergic agents, we examined the effects of cholinergic agonists and antagonists on the enzyme and found none. The possibility that the inhibition of this enzyme by lithium ion is related to the pharmacological actions of lithium is discussed.