Biosynthesis of cholesterol and other sterols.
Biosynthesis of cholesterol and other sterols.
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DOI：
10.1021/cr200021m
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发表时间：
2011-10-12
期刊：
影响因子：
62.1
通讯作者：
Nes, W. David
中科院分区：
文献类型：
--
作者：
Nes, W. David
胆固醇及其具有 1, 2-环戊全氢菲环系统（图 1）的同类物质形成甾体组，该组包含一个化学库，其中包含在所有形式的真核生物和一些原核生物中发现的 1000 多种天然产物，具有多种生物功能。 1, 2 这些化合物的结构和立体化学共性在很大程度上源自产生母体甾醇框架的氧化角鲨烯合酶（以前称为环化酶）的作用。布朗和戈德斯坦在 1985 年的诺贝尔奖演讲中表示，“胆固醇是生物学中最受尊敬的小分子”，这一观点得到了许多诺贝尔奖的支持，这些诺贝尔奖授予那些将一生中大部分时间用于研究甾醇、其代谢物或其他类异戊二烯的化学和化学生物学的一个或多个方面的个人。 2, 3 第一种已知的甾醇——胆固醇，是法国化学家在 230 多年前发现的，它是人类胆结石的结晶成分。 1789 年，Francois Poulletier de La Salle 观察到了胆汁结石中的醇溶部分，10 年后 De Fourcroy 报告称，该部分与腐烂尸体脂肪中的蜡状物质（称为脂肪脂）相同。 4 此后不久，Michel Chevreul 确定胆结石的结晶成分的熔点为 137°C（公认的胆固醇熔点为 149°C），与脂肪或来自鲸鱼的另一种蜡质材料鲸蜡（其熔点为 44-68°C）不同，并用两个希腊词将其命名为“胆固醇”：chole，意思是胆汁和 立体声，意思是坚固。 4, 5 在英语国家，在认识到该物质是仲醇后，胆固醇这一名称被替换为胆固醇。胆固醇的正确分子式（C27H45OÀ，这里显示它有一个羟基，尽管它含有 46 个氢原子）是由 F. Reinitze 于 1888 年提出的，但又花了 30 年的时间才建立了该分子的精确空间表示，这一努力为 Wieland (1927) 和 Windaus (1928) 赢得了诺贝尔化学奖。胆固醇与人类健康之间的首次联系出现在 1843 年，当时沃格尔发现动脉斑块中存在胆固醇。 5 随后确定胆固醇广泛分布于动物界，其异构形式（称为“胆固醇体”或植物甾醇）在植物界也很常见。 6 这些对甾醇天然产物调查的早期尝试是基于熔点、颜色反应、旋光度和晶形的测量。甾醇研究在 20 世纪中后期发生了变化，集中于仿生化学、示踪剂工作、酶学以及使用高场 NMR 和 X 射线衍射方法确定结构，最终得出了胆固醇合成的大致轮廓以及作用于羊毛甾醇和胆固醇之间的所有微粒体结合酶的部分或完全纯化。 7-13 麦角甾醇，然后是胆固醇，被发现发挥与膜（体积作用）和信号（火花）功能相关的多种细胞作用，这些作用可以通过化合物的结构和数量来区分； 14-17 尤其是甾醇在培养的植物和动物细胞中累积量约为 3000 fg/细胞，在酵母中累积量为 20 fg/细胞。 18 期间
Cholesterol and its relatives possessing the 1, 2-cyclopentanoperhydrophenanthrene ring system (Figure 1) form the sterolome, which comprises a chemical library of more than 1000 natural products found in all forms of eukaryotes and some prokaryotes that serve a myriad of biological functions. 1, 2 The structural and stereochemical commonality of these compounds derive in large part from the action of oxidosqualene synthases (formerly cyclases) that generate the parent sterol frame. In their 1985 Nobel lecture, Brown and Goldstein stated that “cholesterol is the most highly decorated small molecule in biology”, a comment supported by the many Nobel prizes awarded to individuals who devoted a large part of their lives to research one or more aspects of the chemistry and chemical biology of sterols, their metabolites, or other isoprenoids. 2, 3 The first known sterol, cholesterol, was discovered by French chemists as a crystalline component of human gallstones over 230 years ago. In 1789, Francois Poulletier de La Salle observed an alcohol-soluble portion of bile stones, which 10 years later was reported by De Fourcroy to be identical to a waxy material in the fat of putrefied corpses referred to as adipocire. 4 Shortly thereafter, Michel Chevreul established that the crystalline component of bile stones, which gave a melting point of 137 C (accepted mp for cholesterol is 149 C), was distinct from adipocire or that of another waxy material from whale, spermaceti (their mp ranged 44À68 C), and named it “cholesterine” from two Greek words: chole, meaning bile and stereos, meaning solid. 4, 5 In English-speaking countries, the name cholesterin was replaced with cholesterol after recognition that the substance was as a secondary alcohol. The correct formula (C27H45OÀ, which here shows that it has a hydroxyl group although it contains 46 hydrogen atoms) of cholesterol was proposed in 1888 by F. Reinitze, yet it took another 30 years to establish the exact steric representation of the molecule, efforts that led to the Nobel Prizes in chemistry for Wieland (1927) and Windaus (1928). The first connection between cholesterol and human health appeared in 1843 as Vogel showed that cholesterol was present in arterial plaques. 5 Cholesterol was subsequently determined to be widely distributed in the animal kingdom and its isomeric forms, termed “cholesterol bodies” or phytosterol, were shown to frequent the vegetable kingdom. 6 These early attempts at natural product surveys of sterols were based on measurements of melting point, color reaction, optical rotation, and crystalline form. Sterol research changed in the mid-to late 20th century and centered on biomimetic chemistry, tracer work, enzymology, and structure determination using high-field NMR and X-ray diffraction methods, culminating with a broad outline for cholesterol synthesis and the partial or complete purification of all the microsomal-bound enzymes that act on sterols between lanosterol and cholesterol. 7À13 Ergosterol, then cholesterol, was discovered to play multiple cellular roles associated with membrane (bulk role) and signal (sparking) functions, which could be differentiated by structure and amount of compound; 14À17 notably sterols accumulate in cultured plant and animal cells at approximately 3000 fg/cell and in yeast at 20 fg/cell. 18 During
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影响因子：
56.9
作者：
BROWN, MS;GOLDSTEIN, JL
通讯作者：
GOLDSTEIN, JL
影响因子：
4.1
作者：
AKHTAR, M;CALDER, MR;WRIGHT, JN
通讯作者：
WRIGHT, JN
影响因子：
15
作者：
Blagg, BSJ;Jarstfer, MB;Poulter, CD
通讯作者：
Poulter, CD
影响因子：
7.3
作者：
ATOR, MA;SCHMIDT, SJ;BARONE, JM
通讯作者：
BARONE, JM
影响因子：
5.1
作者：
AKHTAR, M;FREEMAN, CW;WILTON, DC
通讯作者：
WILTON, DC