无机多磷酸盐作为细胞外基质中代谢能量的储存和发生器。,Chemical Reviews

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无机多磷酸盐作为细胞外基质中代谢能量的储存和发生器。
Chemical Reviews ( IF 51.4 ) Pub Date : 2019-11-18 , DOI: 10.1021/acs.chemrev.9b00460
Werner E G Müller ₁ , Heinz C Schröder ₁ , Xiaohong Wang ₁

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无机聚磷酸盐 (polyP) 由正磷酸盐残基的线性链组成，通过高能磷酸酐键连接。它们是进化上古老的生物聚合物，从细菌到人类都存在。没有其他分子能像聚磷那样集中（生物）化学可用能量。然而，这种长期被忽视的聚合物的功能和代谢却鲜为人知，尤其是在高等真核生物中。近年来，随着发现聚磷作为骨矿化中的磷酸盐来源，人们对聚磷的兴趣重新兴起。后来，两项发现使polyP成为再生医学应用的焦点。首先，polyP表现出形态发生活性，即通过基因诱导诱导细胞分化，其次，在细胞外空间中充当能量储存和供体。对酸性钙体和线粒体的研究首次深入了解了真核多聚磷形成的酶促基础。此外，碱性磷酸酶和腺苷酸激酶的协同作用被证明对于 PolyP 生成 ADP/ATP 至关重要。将 PolyP 添加到哺乳动物细胞的细胞外，导致 ATP 增加 3 倍。讨论了这种磷酸转移反应对于细胞外基质中能量消耗过程的重要性和机制。本综述旨在对这种能够储存（生物）化学有用能量的独特聚合物的形成和功能进行批判性概述。

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Inorganic Polyphosphates As Storage for and Generator of Metabolic Energy in the Extracellular Matrix.

Inorganic polyphosphates (polyP) consist of linear chains of orthophosphate residues, linked by high-energy phosphoanhydride bonds. They are evolutionarily old biopolymers that are present from bacteria to man. No other molecule concentrates as much (bio)chemically usable energy as polyP. However, the function and metabolism of this long-neglected polymer are scarcely known, especially in higher eukaryotes. In recent years, interest in polyP experienced a renaissance, beginning with the discovery of polyP as phosphate source in bone mineralization. Later, two discoveries placed polyP into the focus of regenerative medicine applications. First, polyP shows morphogenetic activity, i.e., induces cell differentiation via gene induction, and, second, acts as an energy storage and donor in the extracellular space. Studies on acidocalcisomes and mitochondria provided first insights into the enzymatic basis of eukaryotic polyP formation. In addition, a concerted action of alkaline phosphatase and adenylate kinase proved crucial for ADP/ATP generation from polyP. PolyP added extracellularly to mammalian cells resulted in a 3-fold increase of ATP. The importance and mechanism of this phosphotransfer reaction for energy-consuming processes in the extracellular matrix are discussed. This review aims to give a critical overview about the formation and function of this unique polymer that is capable of storing (bio)chemically useful energy.

更新日期：2019-11-18

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