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首页> 外文期刊>Biochemistry >Functional Energetic Landscape in the Allosteric Regulation of Muscle Pyruvate Kinase. 3. Mechanism
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Functional Energetic Landscape in the Allosteric Regulation of Muscle Pyruvate Kinase. 3. Mechanism

机译：丙酮酸激酶激酶的变构调节中的功能性能量景观。 3.机制

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摘要

ABSTRACT: Mammalian pyruvate kinase exists in four isoforms with characteristics tuned to specific metabolicnrequirements of different tissues. All of the isoforms, except themuscle isoform, exhibit typical allosteric behavior.nThe case of themuscle isoformis a conundrum. It is inhibited by an allosteric inhibitor, Phe, yet it has traditionallynnot been considered as an allosteric enzyme. In this series of study, an energetic landscape of rabbit musclenpyruvate kinase (RMPK) was established. The phenomenon of inhibition by Phe is shown to be physiological.nFurthermore, the thermodynamics for the temperature fluctuation and concomitant pHchange as a consequencenofmuscle activity were elucidated.We have shown that (1) the differential number of protons released or absorbednwith regard to the various linked reactions adds another level of control to shift the binding constants andnequilibrium of active/inactive state changes (the latter controls quantitatively the activity of RMPK); (2) ADPnplays a major role in the allosteric mechanism in RMPK under physiological temperatures (depending on thentemperature, ADP can assume dual and opposite roles of being an inhibitor by binding preferentially to theninactive form and a substrate); and (3) simulation of the RMPK behavior under physiological conditions showsnthat the net results of the 21 thermodynamic parameters involved in the regulation are well-tuned to allow thenmaximal response of the enzyme to even minute changes in temperature and ligand concentration.
机译：摘要：丙酮酸丙酮酸激酶以四种亚型存在，其特征可根据不同组织的特定代谢需要进行调整。除肌肉同工型外，所有同工型均表现出典型的变构行为。n肌肉同工型是一个难题。它被一种变构抑制剂Phe抑制，但是传统上它并未被认为是一种变构酶。在这一系列研究中，建立了兔肌肉丙酮酸激酶（RMPK）的能量图。 Phe抑制的现象被证明是生理性的。此外，阐明了由于肌肉活动而引起的温度波动和随之而来的pH变化的热力学。我们已经表明（1）各种键之间释放或吸收的质子的数量不同。反应增加了另一种控制水平，以改变结合常数和平衡活性/非活性状态的变化（后者定量地控制RMPK的活性）； （2）在生理温度下，ADPn在RMPK的变构机制中起主要作用（取决于当时的温度，ADP可以通过优先结合非活性形式和底物而承担起抑制剂的双重和相反作用）； （3）在生理条件下对RMPK行为的模拟表明，调节中涉及的21个热力学参数的最终结果是经过微调的，从而可以使酶对温度和配体浓度的微小变化产生最大响应。

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  • 来源
    《Biochemistry》 |2009年第40期|p.9466-9470|共5页
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    Petr Herman* and J. Ching Lee;

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    ‡Faculty of Mathematics and Physics, Institute of Physics, Charles University, Ke Karlovu 5, 121 16 Prague, Czech Republic, and§Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555-1055;

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