在金属蛋白中,Li+和Mg2+之间的竞争. 对疗法的影响
1Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan. todor@ibms.sinica.edu.tw
Journal of the American Chemical Society
|May 21, 2011
概括
离子 (Li+) 通过与离子 (Mg2+) 竞争来选择性抑制双相情感障碍治疗中的酶. 这种选择性源于特定的蛋白质结合部位特征,而不是一般的细胞Mg2+需求.
科学领域:
- 生物化学 生物化学
- 神经科学是一个神经科学.
- 药理学 药理学 是一个学科.
背景情况:
- 盐是双相情感障碍的主要治疗方法,并被用于研究神经退行性疾病,如阿尔茨海默氏症和帕金森症.
- 一个关于作用的拟议机制涉及离子 (Li+) 和离子 (Mg2+) 之间在酶结合位点上的竞争.
- 了解特定酶中Li+对Mg2+的选择性对于解释的治疗作用和潜在副作用至关重要.
研究的目的:
- 调查决定特定酶中Mg2+被Li+选择性取代的因素.
- 为了阐明为什么Li+抑制了与双相情感障碍相关的酶,但不抑制细胞必需的Mg2+依赖蛋白质.
- 确定金属结合点的结构和化学特性,从而使Li+比Mg2+具有选择性.
主要方法:
- 对金属结合部位的计算分析,考虑诸如净电荷,配体组成和溶剂暴露等因素.
- 对负电荷氨基酸 (Asp/Glu) 和溶剂可访问性在蛋白质选择性中的作用的评估.
- 对细胞Mg2+恒温机制的分析,包括Mg2+与其他离子 (Ca2+,Zn2+) 的度比率.
主要成果:
- 2+和+之间的竞争取决于金属复合物的净电荷和结合腔的溶剂暴露.
- 蛋白质选择Mg2+而不是Li+通过利用富含负电荷残留物 (Asp/Glu) 的溶剂不可访问的结合点.
- 细胞通过调节不同区间的Mg2+度比率来维持Mg2+对其他双价的选择性.
结论:
- 的治疗选择性源于其仅在具有有利电荷和可访问性特征的特定酶结合位点取代Mg2+的能力.
- 基本的Mg2+依赖性蛋白质因其独特的结合位属性和细胞Mg2+度而受到Li+干扰的保护.
- 这项研究为在双相情感障碍中的疗效及其对关键细胞功能的相对安全性提供了机制性的解释.
相关概念视频
02:51Metal-Ligand Bonds
The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
00:56Extraction: Advanced Methods
Metal ions can be separated from one another by complexation with organic ligands–the chelating agent– to form uncharged chelates. Here, the chelating agent must contain hydrophobic groups and behave as a weak acid, losing a proton to bind with the metal. Since most organic ligands used in this process are insoluble or undergo oxidation in the aqueous phase, the chelating agent is initially added to the organic phase and extracted into the aqueous phase. The metal-ligand complex is formed in...
01:09Complexation Equilibria: Factors Influencing Stability of Complexes
In complexation reactions, metal cations are the electron pair acceptors, and the ligands are the electron pair donors. The stability of the metal complexes depends primarily on the complexing ability of the central metal ion and the nature of the ligands. Generally, the complexing ability of the metal ion depends on the size and charge of the ion. As the metal ion size increases, the stability of the metal complexes decreases, provided that the valency of the metal ion and the ligands remain...
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
01:19Ligand-gated Ion Channels
Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
01:24Mania and Antimanic Drugs: Overview
Mania, a psychological condition characterized by elevated mood, increased energy, and reduced sleep need, is part of the bipolar disorder cycle. The exact cause of mania isn't entirely known, but it is thought to be a combination of genetic, environmental, and neurological factors. Bipolar disorder involves alternating manic and depressive episodes. Mood stabilizers like lithium, antipsychotics, and anticonvulsants help manage these episodes. Lithium carbonate is particularly effective as a...