首页> 外文期刊>The journal of physical chemistry, B. Condensed matter, materials, surfaces, interfaces & biophysical >Role of Cholesterol and Its Immediate Biosynthetic Precursors in Membrane Dynamics and Heterogeneity: Implications for Health and Disease
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Role of Cholesterol and Its Immediate Biosynthetic Precursors in Membrane Dynamics and Heterogeneity: Implications for Health and Disease

机译:胆固醇及其直接生物合成前体在膜动力学和异质性中的作用:健康与疾病的影响

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Cholesterol is an indispensiblc component of cellular membranes in higher eukaryotes and plays a vital role in many cellular functions. 7-Dehydrocholesterol (7-DHC) and desmosterol represent two immediate biosynthetic precursors of cholesterol in the Kandutsch-Russell and Bloch pathways of cholesterol biosynthesis, respectively. Although 7-DHC and desmosterol differ from cholesterol merely by a double bond, accumulation of these two immediate biosynthetic precursors due to defective cholesterol biosynthesis leads to severe developmental and neurological disorders. In this context, we explored the role of cholesterol and its immediate biosynthetic precursors (7-DHC and desmosterol) on the dynamics and heterogeneity of fluid phase POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and gel phase DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) membranes, using fluorescence lifetime distribution analysis of Nile Red (9-diethylamino-5H-benzo[alpha]phenoxazine-5-one) using the maximum entropy method (MEM). We show here that the membrane interfacial dynamic heterogeneity, manifested as the width of the fluorescence lifetime distribution of Nile Red, exhibited by 7-DHC and desmosterol vastly differ from that displayed by cholesterol, particularly in fluid phase membranes. We conclude that a subtle alteration in sterol structure could considerably alter dynamic membrane heterogeneity, which could have implications in pathogenicity associated with defective cholesterol biosynthesis.
机译:胆固醇是在较高真核生物中的细胞膜的吲缺性组分,在许多细胞功能中起着至关重要的作用。 7-脱羟基醇(7-DHC)和Desmosterol分别代表了胆固醇生物合成的Kandutsch-Russell和Bloch途径中的两个直接生物合成前体。虽然7-DHC和Desmosterols仅仅通过双键不同于胆固醇,但由于胆固醇生物合成缺陷导致这两个直接生物合成前体的积累导致严重发育和神经系统疾病。在这方面,我们探索了胆固醇和它的直接生物合成前体(7-DHC和24-脱氢)上流体相POPC(1-棕榈酰-2-油酰-sn-甘油-3-磷酸胆碱)和凝胶的动态和异质性的作用通过最大熵方法,使用最大熵方法使用尼罗红(9-二乙基氨基-5H-苯并α-苯氧胺-5-一)的荧光寿命分布分布分布分布分析分析(1,2-二甲基-5H-苯并α)膜( MEM)。我们在这里表明,该膜界面动态异质,表现为尼罗红的荧光寿命分布的宽度,由7-DHC表现出24-脱氢和大大不同于由胆固醇所显示的不同,特别是在流体相的膜。我们得出结论,甾醇结构的微妙改变可以大大改变动态膜异质性,这可能对缺陷胆固醇生物合成相关的致病性有影响。

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