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腺苷作为组织功能的代谢调节剂:胞质5'-核苷酸酶产生腺苷。

Adenosine as a metabolic regulator of tissue function: production of adenosine by cytoplasmic 5'-nucleotidases.

作者信息

Borowiec Agnieszka, Lechward Katarzyna, Tkacz-Stachowska Kinga, Składanowski Andrzej C

机构信息

Department of Molecular Enzymology, Intercollegiate Faculty of Biotechnology UG-MUG, Medical University of Gdańsk, Gdańsk, Poland.

出版信息

Acta Biochim Pol. 2006;53(2):269-78. Epub 2006 Jun 12.

PMID:16770441
Abstract

Adenosine is a product of complete dephosphorylation of adenine nucleotides which takes place in various compartments of the cell. This nucleoside is a significant signal molecule engaged in regulation of physiology and modulation of the function of numerous cell types (i.e. neurons, platelets, neutrophils, mast cells and smooth muscle cells in bronchi and vasculature, myocytes etc.). As part a of purinergic signaling system, adenosine mediates neurotransmission, conduction, secretion, vasodilation, proliferation and cell death. Most of the effects of adenosine help to protect cells and tissues during stress conditions such as ischemia or anoxia. Adenosine receptors and nucleoside transporters are targets for potential drugs in many pathophysiological situations. The adenosine-producing system in vertebrates involves a cascade dephosphorylating ATP and ending with 5'-nucleotidase (EC 3.1.3.5) localized either on the membrane or inside the cell. In this paper the cytoplasmic variants of 5'-nucleotidase are broadly characterized as well as their clinical relevance. The role of AMP-selective 5'-nucleotidase (cN-I) in the heart, skeletal muscle and brain is highlighted. cN-I action is crucial during ischemia and important for the efficacy of some nucleoside-based drugs and in the regulation of the substrate pool for nucleic acids synthesis. Inhibitors used in studying the roles of cytoplasmic and membrane-bound 5'-nucleotidases are also described.

摘要

腺苷是腺嘌呤核苷酸在细胞各个区室中完全去磷酸化的产物。这种核苷是一种重要的信号分子,参与多种细胞类型(如神经元、血小板、中性粒细胞、肥大细胞以及支气管和脉管系统中的平滑肌细胞、心肌细胞等)的生理调节和功能调节。作为嘌呤能信号系统的一部分,腺苷介导神经传递、传导、分泌、血管舒张、增殖和细胞死亡。腺苷的大多数作用有助于在缺血或缺氧等应激条件下保护细胞和组织。在许多病理生理情况下,腺苷受体和核苷转运体是潜在药物的作用靶点。脊椎动物体内的腺苷生成系统涉及一个使ATP去磷酸化的级联反应,最终以定位在细胞膜上或细胞内的5'-核苷酸酶(EC 3.1.3.5)结束。本文对5'-核苷酸酶的胞质变体及其临床相关性进行了广泛描述。重点介绍了AMP选择性5'-核苷酸酶(cN-I)在心脏、骨骼肌和大脑中的作用。cN-I的作用在缺血期间至关重要,对某些核苷类药物的疗效以及核酸合成底物池的调节也很重要。还介绍了用于研究胞质和膜结合5'-核苷酸酶作用的抑制剂。

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