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有机渗透溶质作为高渗及其他应激状态下的相容性、代谢性及对抗性细胞保护剂。

Organic osmolytes as compatible, metabolic and counteracting cytoprotectants in high osmolarity and other stresses.

作者信息

Yancey Paul H

机构信息

Biology Department, Whitman College, Walla Walla, WA 99362, USA.

出版信息

J Exp Biol. 2005 Aug;208(Pt 15):2819-30. doi: 10.1242/jeb.01730.

DOI:10.1242/jeb.01730
PMID:16043587
Abstract

Organic osmolytes are small solutes used by cells of numerous water-stressed organisms and tissues to maintain cell volume. Similar compounds are accumulated by some organisms in anhydrobiotic, thermal and possibly pressure stresses. These solutes are amino acids and derivatives, polyols and sugars, methylamines, methylsulfonium compounds and urea. Except for urea, they are often called ;compatible solutes', a term indicating lack of perturbing effects on cellular macromolecules and implying interchangeability. However, these features may not always exist, for three reasons. First, some of these solutes may have unique protective metabolic roles, such as acting as antioxidants (e.g. polyols, taurine, hypotaurine), providing redox balance (e.g. glycerol) and detoxifying sulfide (hypotaurine in animals at hydrothermal vents and seeps). Second, some of these solutes stabilize macromolecules and counteract perturbants in non-interchangeable ways. Methylamines [e.g. trimethylamine N-oxide (TMAO)] can enhance protein folding and ligand binding and counteract perturbations by urea (e.g. in elasmobranchs and mammalian kidney), inorganic ions, and hydrostatic pressure in deep-sea animals. Trehalose and proline in overwintering insects stabilize membranes at subzero temperatures. Trehalose in insects and yeast, and anionic polyols in microorganisms around hydrothermal vents, can protect proteins from denaturation by high temperatures. Third, stabilizing solutes appear to be used in nature only to counteract perturbants of macromolecules, perhaps because stabilization is detrimental in the absence of perturbation. Some of these solutes have applications in biotechnology, agriculture and medicine, including in vitro rescue of the misfolded protein of cystic fibrosis. However, caution is warranted if high levels cause overstabilization of proteins.

摘要

有机渗透物是许多处于水分胁迫的生物体和组织的细胞用来维持细胞体积的小分子溶质。一些生物体在脱水、热胁迫以及可能的压力胁迫下会积累类似的化合物。这些溶质包括氨基酸及其衍生物、多元醇和糖类、甲胺、甲基锍化合物和尿素。除尿素外,它们通常被称为“相容性溶质”,该术语表示对细胞大分子没有干扰作用,并意味着具有互换性。然而,由于三个原因,这些特性可能并非总是存在。首先,其中一些溶质可能具有独特的保护性代谢作用,例如作为抗氧化剂(如多元醇、牛磺酸、亚牛磺酸)、提供氧化还原平衡(如甘油)以及使硫化物解毒(热液喷口和渗漏处动物体内的亚牛磺酸)。其次,其中一些溶质以不可互换的方式稳定大分子并抵消干扰物。甲胺[如氧化三甲胺(TMAO)]可以增强蛋白质折叠和配体结合,并抵消尿素(如在板鳃亚纲动物和哺乳动物肾脏中)、无机离子以及深海动物体内静水压力的干扰。越冬昆虫体内的海藻糖和脯氨酸在零下温度下稳定细胞膜。昆虫和酵母中的海藻糖以及热液喷口周围微生物中的阴离子多元醇可以保护蛋白质免受高温变性。第三,稳定溶质在自然界中似乎仅用于抵消大分子的干扰物,这可能是因为在没有干扰的情况下稳定作用是有害的。其中一些溶质在生物技术、农业和医学中有应用,包括对囊性纤维化错误折叠蛋白的体外挽救。然而,如果高浓度导致蛋白质过度稳定,则需要谨慎使用。

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