Noncholesterol sterols。

Marek Vecka, Ales Zak, Eva Tvrzická
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引用次数: 0

摘要

虽然我们大多数人都或多或少熟悉“胆固醇”这个词,但固醇的世界要复杂得多,也有趣得多。除了胆固醇,在人的血浆中还可以发现许多非胆固醇固醇,这些固醇在人体有机体中起着许多重要的作用。它们要么来自内源性胆固醇的生物合成,要么来自膳食来源(植物甾醇)。唯一的胆固醇分子用于保持我们细胞膜的健康,用于信号传递的目的,以及胆汁酸和类固醇激素的前体。在其生物合成途径中,胆固醇之前的化合物被确定为维生素D3前体,减数分裂激活甾醇,现在看来它们可能在胆固醇稳态中起作用。从植物中摄取的甾醇,即植物甾醇,从肠细胞中排出,从而间接帮助我们的肠道应对管腔中大量的胆固醇。高等植物合成许多植物甾醇,但在海洋生物中,我们可以发现其他数量不多的甾醇分子。甾醇分子的多样性及其四环核心对酶活性的抗性表明,甾醇在多细胞生物的个体发生过程中具有至关重要的作用。第一次氧气出现在地球上是在27亿年前,从那时起,每一种新的生命形式都利用了氧气,这也是固醇分子形成所需要的。过去的几十年改变了我们对固醇分子在人体中几乎所有层面上的外观的看法。在肠道中,甾醇的吸收被证明是蛋白质依赖的,对转运体的探索是成功的。细胞内胆固醇稳态的一般概念已经被描述,包括迄今为止难以置信的共价相互作用-胆固醇和蛋白质。随着人们努力发现动脉粥样硬化的根本原因,非胆固醇固醇的临床重要性也在上升。所讨论的化合物胆固醇似乎与此有关,但它本身听起来并不重要。谷甾醇血症中植物甾醇的积累增加了动脉粥样硬化早期发生的可能性,这一事实进一步支持了一些甾醇(或类固醇)化合物在分子水平上负责触发导致动脉粥样硬化的病理生化级联事件的假设。了解甾醇在肠细胞吸收过程中发生的过程,导致在甾醇转运到肠细胞、甾醇酯化和乳糜微粒堆积水平上合成选择性抑制剂,这些都处于临床试验的不同阶段。本专著最后一部分的研究代表了非胆固醇固醇分析的临床潜力。在定义明确的群体中,这些分析物使我们能够评估胆固醇稳态的变化,这可以反映在总胆固醇的浓度中。此外,某些血浆固醇的高浓度可能表明胆固醇生物合成(Smith-Laemli-Opitz综合征)、运输(谷固醇血症)或代谢(脑腱黄瘤病)的先天性错误。关于非胆固醇类甾醇研究的一些问题仍未得到解答,如胆固醇生物合成的一些酶(seladin-1、甾醇D14还原酶)为何具有其他功能,甾醇吸收的定性方面尚未得到令人满意的解释,以及植物甾醇从人体排出的确切原因尚不清楚。然而,作者希望所呈现的事实可以拓宽读者对这一区域的看法,这一区域通常隐藏在胆固醇分子之下。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Noncholesterol sterols.

Although most of us are more or less familiar with the term "cholesterol", the world of sterols is far more complicated and interesting. Apart from cholesterol, many non-cholesterol sterols can be found in human plasma and these sterols serve many important functions in human organism. They are either derived from endogenous biosynthesis of cholesterol or they come from dietary sources (phytosterols). The sole cholesterol molecule is used for keeping our cell membranes fit, for signalization purposes as well as a precursor for bile acids and steroid hormones. The compounds prior to cholesterol in its biosynthetic pathway were identified as vitamin D3 precursor, meiosis activating sterols and nowadays it seems that they could play a role in cholesterol homeostasis. The sterols from ingested vegetable sources, the phytosterols, are expelled from enterocytes and thus indirectly help our gut in coping with abundant cholesterol in the lumen. Higher plants synthesize many phytosterols, but in marine organisms, we can find other innumerous sterol molecules. The diversity of sterol molecules produced and resistance of their tetracyclic core to enzymatic activities implies crucial importance of sterols during the ontogenesis of multicellular organisms. First oxygen appeared on the Earth app. 2.7 billion years ago and since that time, every new life form took the advantage of oxygen needed also for build-up of sterol molecules. The last decades changed our view to the sterol molecules on almost at all levels of their appearance in human body. In the gut, the absorption of sterols was proven to be protein dependent and the quest for the transporter was successful. The general concepts of intracellular homeostasis of cholesterol have been described including the covalent interaction unbelievable so far - cholesterol and a protein. The clinical importance of non-cholesterol sterols rises with the effort to discover underlying facts about the causes of atherosclerosis. The compound in question, cholesterol, seems to be involved, but it sounds not to be crucial per se. The fact that the accumulation of phytosterols in sitosterolemia enhances the probability of early atherosclerosis onset further supports the hypothesis about some sterol (or steroid) compound being responsible on the molecular level for triggering the pathobiochemical cascade of events leading to atherosclerosis. Understanding the processes taking place in the enterocyte during the absorption of sterols resulted in synthesis of selective inhibitors at the level of sterol translocation into the enterocyte, sterol esterification and chylomicron packing, which are in different phases of clinical testing. The studies in the last part of the monograph represent the clinical potential of the analyses of non-cholesterol sterols. In well-defined groups, these analytes enables us to assess the changes in the homeostasis of cholesterol, which can be reflected in the concentration of total cholesterol. Furthermore, the high concentrations of some plasma sterols could point to the inborn errors of cholesterol biosynthesis (Smith-Laemli-Opitz syndrome), transport (sitosterolemia) or metabolization (cerebrotendinous xanthomatosis). Some issues concerning the research on the non-cholesterol sterols still remain unanswered - it is not known why some of the enzymes of the cholesterol biosynthesis (seladin-1, sterol D14 reductase) have other functions, qualitative aspects of sterol absorption are not satisfactorily explained and exact reason for expulsion of phytosterols from human body is not clear. Nevertheless, the authors hope that the presented facts can broaden the reader's perspective about the area, which is usually hidden beneath the cholesterol molecule.

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