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RUI: Evolution of Cholinesterase In Vivo and In Vitro

RUI: Evolution of Cholinesterase In Vivo and In Vitro
RUI:胆碱酯酶体内外的进化
批准号:
9319354
负责人:
Leo Pezzementi
金额:
$11.17万
依托单位:
依托单位国家:
美国
项目类别:
Standard Grant
财政年份:
1994
资助国家:
美国
项目状态:
已结题
起止时间:
1994-05-15 至 1998-04-30

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中文摘要
翻译
当一个人运动肌肉时,乙酰胆碱酯酶通过分解神经递质乙酰胆碱来确保肌肉放松,乙酰胆碱是由神经系统释放的,启动肌肉收缩的过程。因此,所有的运动活动都需要乙酰胆碱酯酶,包括写作和说话。除了乙酰胆碱酯酶,人类还拥有另一种进化相关的酶,丁基胆碱酯酶,具有相似但不同的特征。与乙酰胆碱酯酶相反,这种酶的功能是未知的。事实上,有些人似乎完全缺乏这种酶,但看起来很正常。有人认为,丁基胆碱酯酶作为摄入的神经毒素的清道夫,并在神经系统的胚胎发育中发挥作用。尽管人类和其他高等脊椎动物同时拥有两种胆碱酯酶,但低等脊椎动物似乎只拥有一种乙酰胆碱酯酶。无脊椎动物也只有一种胆碱酯酶;但它既不是乙酰胆碱酯酶,也不是丁基胆碱酯酶,而是一种具有中间特性的酶。有人说:“生物学中没有任何东西是有意义的,除非从进化的角度来看。”因此,为了阐明这两种胆碱酯酶在人类中的作用,特别是丁基胆碱酯酶,Pezzementi博士正在追踪这两种酶的进化,使用生物化学、药理学和重组DNA技术来研究选定生物体中胆碱酯酶的结构和功能,从单一的中间胆碱酯酶转变为两种不同的胆碱酯酶。将这些信息与相关生物体的生物学结合起来,可以为这些酶的生理功能提供进一步的线索。***
英文摘要
9319354 Pezzementi Whenever one moves a muscle, the enzyme acetylcholinesterase insures that the muscle will relax by breaking down the neurotransmitter acetylcholine, which is released by the nervous system initiating the processes of muscle contraction. Thus, acetylcholinesterase is required for all motor activity, including writing and speech. In addition to acetylcholinesterase, humans possess another evolutionarily related enzyme, butyrylcholinesterase, with similar, but distinct, characteristics. In contrast to acetylcholinesterase, the function of this enzyme is unknown. In fact, there appear to be individuals who lack this enzyme entirely, yet appear normal. It has been suggested that butyrylcholinesterase acts as a scavenger of ingested neurotoxins and that it plays a role in the embryological development of the nervous system. Although humans and other higher vertebrates possess both cholinesterases, lower vertebrates appear to possess only one, acetylcholinesterase. Invertebrates also possess only one cholinesterase; however, it is neither acetylcholinesterase, nor butyrylcholinesterase, but an enzyme with intermediate characteristics. It has been stated that "nothing in biology makes sense, except in the light of evolution." Thus, in an attempt to clarify the roles of the two cholinesterases in humans, in particular butyrylcholinesterase, Dr. Pezzementi is tracing the evolution of the two enzymes, using the techniques of biochemistry, pharmacology, and recombinant DNA technology to study the structure and function of cholinesterases in selected organisms, where the transition from a single intermediate cholinesterase to two distinct cholinesterases occurs. Integration of this information with the biology of the organisms in question could provide further clues about the physiological functions of these enzymes. ***
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