FUNCTION OF CARDIOLIPIN PHASE POLYMORPHISM

在低盐条件下，心磷脂可以从片层相转变 在高盐条件下，浓度为六方II相。酰基 心磷脂和单溶心磷脂保持六角形II相或 分别与盐浓度无关的片层(Powell& 《生物化学》24(1985)2902-2908)。层状结构的影响- 偏爱二油酰磷脂酰胆碱(DOPC)等脂类 存在固有的细胞膜酶，细胞色素氧化酶， 这些相变将使用31P-核磁共振、低角X-射线扫描进行评估。 X射线衍射和冷冻断口电子显微镜 与Max-Planck生物物理研究所D.Marsh合作 化学。DOPC与上述混合物的渗透性 心磷脂作为钠、钾和11-Will的大单层囊泡 然后在相行为被测量的条件下 已知的和掺入细胞色素氧化酶对这些的影响 观察到渗透性。结果将证明 脂蛋白-界面的封闭效率和 形成非片层相的脂类的存在的重要性 与这些相关的膜特性有关。在心脏组织中的溶固脂 在心肌梗死期间形成的可能使内部 线粒体膜渗漏、解偶联电子传递和 磷酸化直接导致细胞死亡。游行示威 在这种情况下细胞死亡的分子基础 将更好地干预和治疗专利 心脏病。

Cardiolipin can be shifted from lamellar phase in low salt concentrations to hexagonal II phase in high salt. Acyl cardiolipin and monolysocardiolipin remain hexagonal II phase or lamellar respectively independent of salt concentration (Powell & Marsh, Biochemistry 24 (1985) 2902-2908). The effects of lamellar- favoring lipids like dioleoylphosphatidylcholine (DOPC) and the presence of the intrinsic membrane enzyme, cytochrome oxidase, on these phase changes will be evaluated using 31P-NMR, low angle X- ray diffration, and freeze-fracture electron microscopy in collaboration with D. Marsh, Max-Planck Institute for Biophysical Chemistry. The permeability of mixtures of DOPC and the above cardiolipins as large unilamellar vesicles to Na, K and 11- will then be measured under conditions in which the phase behavior is known and the effect of incorporating cytochrome oxidase on these permeabilities observed. The results will demonstrate the efficiency of sealing at the lipid protein-interface and the importance of the presence of lipids which form non-lamellar phases to these related membrane properties. In heart tissue lysolipids formed during myocardial infarct probably makes the inner mitochondrial membrane leaky, uncoupling electron transport and phosphorylation directly resulting in cell death. Demonstration of the molecular basis of cell death under these circumstances would ensble better intervention and treatment of patents with heart disease.