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人类载脂蛋白和脂蛋白的分子结构与代谢的当前概念。

Current concepts of the molecular structure and metabolism of human apolipoproteins and lipoproteins.

作者信息

Brewer H B

出版信息

Klin Wochenschr. 1981 Sep 15;59(18):1023-35. doi: 10.1007/BF01747745.

DOI:10.1007/BF01747745
PMID:7029129
Abstract

During the last few years major advances have occurred in our knowledge of the structure, function, and metabolism of the plasma lipoproteins. Twelve human apolipoproteins have been isolated and characterized. The primary structure of apolipoproteins A-I, A-II, C-I, C-II, and C-III have been elucidated. The primary structure of these apolipoproteins contain no unique sequences, however the primary structure of several of the apolipoproteins contain segments which can be modeled into amphipathic helices. The helical segments may be important in protein-protein as well as protein-lipid interactions. The molecular properties of the apolipoproteins have been investigated and shown to undergo self-association with major increases in conformation. The molecular organization of the plasma lipoprotein particle has been studied, and an iceberg-sea model has been proposed. This model emphasizes the micellar organization of the phospholipids, and the possibility of secondary, tertiary as well as quaternary structure of the apolipoprotein associated with the lipoprotein particle. The metabolism of plasma lipoproteins has been extensively analyzed over the last several years. Two general types of apolipoprotein-lipoprotein particle interactions have been recognized. The first type involves a "quasi-irreversible" interaction between the apolipoprotein and lipoprotein particle, and is exemplified by apolipoprotein b. The second type of interaction is a "reversible" apolipoprotein-lipoprotein particle interaction. Apolipoproteins a-I, A-II, C-I, C-II, C-III, and E are examples of the reversible interaction. Within this framework two major apoB-lipoprotein particle cascades have been proposed. ApoB-triglyceride rich lipoproteins including chylomicrons and hepatic VLDL undergo sequential triglyceride hydrolysis. Following triglyceride hydrolysis chylomicrons are converted to remnants with hydrated densities principally of VLDL and IDL. Liver apoB-VLDL is converted initially to IDL and finally to LDL. Apolipoproteins which undergo reversible interactions are present in virtually all density fractions and the distribution of these apolipoproteins is determined by the laws of mass action. With these concepts rapid progress has been made in our understanding of apolipoprotein-lipoprotein biochemistry, physiology, and clinical disorders of lipoproteins and atherosclerosis. The next several years will undoubtedly provide further insights into the structure, function, and metabolism of plasma lipoproteins.

摘要

在过去几年中,我们对血浆脂蛋白的结构、功能和代谢的认识取得了重大进展。已分离并鉴定出12种人类载脂蛋白。载脂蛋白A-I、A-II、C-I、C-II和C-III的一级结构已被阐明。这些载脂蛋白的一级结构不包含独特序列,然而,几种载脂蛋白的一级结构包含可模拟为两亲性螺旋的片段。螺旋片段在蛋白质-蛋白质以及蛋白质-脂质相互作用中可能很重要。已对载脂蛋白的分子特性进行了研究,并表明其会发生自缔合,构象有显著增加。已对血浆脂蛋白颗粒的分子组织进行了研究,并提出了冰山-海洋模型。该模型强调了磷脂的胶束组织,以及与脂蛋白颗粒相关的载脂蛋白二级、三级和四级结构的可能性。在过去几年中,对血浆脂蛋白的代谢进行了广泛分析。已认识到两种一般类型的载脂蛋白-脂蛋白颗粒相互作用。第一种类型涉及载脂蛋白与脂蛋白颗粒之间的“准不可逆”相互作用,载脂蛋白b就是一个例子。第二种相互作用类型是“可逆”的载脂蛋白-脂蛋白颗粒相互作用。载脂蛋白a-I、A-II、C-I、C-II、C-III和E是可逆相互作用的例子。在此框架内,已提出了两个主要的载脂蛋白B-脂蛋白颗粒级联反应。富含载脂蛋白B的甘油三酯脂蛋白,包括乳糜微粒和肝脏极低密度脂蛋白(VLDL),会依次进行甘油三酯水解。甘油三酯水解后,乳糜微粒转化为残余物,其水合密度主要为极低密度脂蛋白和中间密度脂蛋白(IDL)。肝脏载脂蛋白B-VLDL最初转化为中间密度脂蛋白,最终转化为低密度脂蛋白(LDL)。发生可逆相互作用的载脂蛋白几乎存在于所有密度组分中,这些载脂蛋白的分布由质量作用定律决定。有了这些概念,我们在理解载脂蛋白-脂蛋白生物化学、生理学以及脂蛋白和动脉粥样硬化的临床疾病方面取得了快速进展。毫无疑问,未来几年将为血浆脂蛋白的结构、功能和代谢提供进一步的见解。

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引用本文的文献

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[The apolipoproteins in man ].[人类中的载脂蛋白]
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