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鹅膏毒素:真菌世界中最具毒性的分子。

Amanitins: The Most Poisonous Molecules of the Fungal World.

作者信息

Vetter János

机构信息

Department of Botany, University of Veterinary Medicine, Pf. 2., 1400 Budapest, Hungary.

出版信息

Molecules. 2023 Aug 7;28(15):5932. doi: 10.3390/molecules28155932.

Abstract

Among the toxic metabolites of the fungal world, those that, due to their strong biological effect, can seriously (even fatally) damage the life processes of humans (and certain groups of animals) stand out. Amatoxin-containing mushrooms and the poisonings caused by them stand out from the higher fungi, the mushrooms. There are already historical data and records about such poisonings, but scientific research on the responsible molecules began in the middle of the last century. The goals of this review work are as follows: presentation of the cosmopolitan mushroom species that produce amanitins (which are known from certain genera of four mushroom families), an overview of the chemical structure and specific properties of amanitins, a summary of the analytical methods applicable to them, a presentation of the "medical history" of poisonings, and a summary of the therapeutic methods used so far. The main responsible molecules (the amanitins) are bicyclic octapeptides, whose structure is characterized by an outer loop and an inner loop (bridge). It follows from the unusual properties of amanitins, especially their extreme stability (against heat, the acidic pH of the medium, and their resistance to human, and animal, digestive enzymes), that they are absorbed almost without hindrance and quickly transported to our vital organs. Adding to the problems is that accidental consumption causes no noticeable symptoms for a few hours (or even 24-36 h) after consumption, but the toxins already damage the metabolism of the target organs and the synthesis of nucleic acid and proteins. The biochemical catastrophe of the cells causes irreversible structural changes, which lead to necrotic damage (in the liver and kidneys) and death. The scientific topicality of the review is due to the recent publication of new data on the probable antidote molecule (ICR: indocyanine green) against amanitins. Further research can provide a new foundation for the therapeutic treatment of poisonings, and the toxicological situation, which currently still poses a deadly threat, could even be tamed into a controllable problem. We also draw attention to the review conclusions, as well as the mycological and social tasks related to amanitin poisonings (prevention of poisonings).

摘要

在真菌界的有毒代谢产物中,那些因其强大的生物效应而能严重(甚至致命)损害人类(以及某些动物群体)生命过程的代谢产物格外突出。含鹅膏毒素的蘑菇及其引发的中毒事件在高等真菌即蘑菇中颇为显著。关于此类中毒事件已有历史资料和记录,但对相关责任分子的科学研究始于上世纪中叶。本综述工作的目标如下:介绍产生鹅膏毒素的世界性蘑菇种类(已知来自四个蘑菇科的某些属),概述鹅膏毒素的化学结构和特殊性质,总结适用于它们的分析方法,呈现中毒事件的“病史”,以及总结迄今所采用的治疗方法。主要责任分子(鹅膏毒素)是双环八肽,其结构的特点是有一个外环和一个内环(桥)。由于鹅膏毒素的特殊性质,尤其是其极高的稳定性(耐热、耐介质的酸性pH值以及对人类和动物消化酶的抗性),它们几乎能毫无阻碍地被吸收并迅速输送到我们的重要器官。更糟糕的是,意外食用后在数小时(甚至24 - 36小时)内不会出现明显症状,但毒素此时已损害目标器官的代谢以及核酸和蛋白质的合成。细胞的生化灾难会导致不可逆转的结构变化,进而引发坏死性损伤(在肝脏和肾脏)并导致死亡。本综述的科学时效性源于近期关于针对鹅膏毒素的可能解毒分子(ICR:吲哚菁绿)的新数据的发表。进一步的研究可为中毒的治疗提供新的基础,当前仍然构成致命威胁的毒理学状况甚至可能被转化为一个可控问题。我们还提请注意综述结论以及与鹅膏毒素中毒相关的真菌学和社会任务(中毒预防)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28fb/10421264/676206045177/molecules-28-05932-g001.jpg

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