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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Generic temperature compensation of biological clocks by autonomous regulation of catalyst concentration
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Generic temperature compensation of biological clocks by autonomous regulation of catalyst concentration

机译：通过自主调节催化剂浓度对生物钟进行通用温度补偿

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Circadian clocks-ubiquitous in life forms ranging from bacteria to multicellular organisms-often exhibit intrinsic temperature compensation; the period of circadian oscillators is maintained constant over a range of physiological temperatures, despite the expected Arrhenius form for the reaction coefficient. Observations have shown that the amplitude of the oscillation depends on the temperature but the period does not; this suggests that although not every reaction step is temperature independent, the total system comprising several reactions still exhibits compensation. Here we present a general mechanism for such temperature compensation. Consider a system with multiple activation energy barriers for reactions, with a common enzyme shared across several reaction steps. The steps with the highest activation energy rate-limit the cycle when the temperature is not high. If the total abundance of the enzyme is limited, the amount of free enzyme available to catalyze a specific reaction decreases as more substrates bind to the common enzyme. We show that this change in free enzyme abundance compensates for the Arrhenius-type temperature dependence of the reaction coefficient. Taking the example of circadian clocks with cyanobacterial proteins KaiABC, consisting of several phosphorylation sites, we show that this temperature compensation mechanism is indeed valid. Specifically, if the activation energy for phosphorylation is larger than that for dephosphor-ylation, competition for KaiA shared among the phosphorylation reactions leads to temperature compensation. Moreover, taking a simpler model, we demonstrate the generality of the proposed compensation mechanism, suggesting relevance not only to circadian clocks but to other (bio)chemical oscillators as well.
机译：昼夜节律生物广泛存在，从细菌到多细胞生物，都具有内在的温度补偿。尽管预期的反应系数为阿伦尼乌斯形式，但在生理温度范围内，昼夜节律振荡器的周期仍保持恒定。观察结果表明，振荡的幅度取决于温度，但周期并不取决于温度。这表明尽管并非每个反应步骤都是与温度无关的，但包括多个反应的整个系统仍表现出补偿性。在这里，我们介绍了这种温度补偿的一般机制。考虑一个具有多个反应激活能垒的系统，在多个反应步骤中共享一种共同的酶。具有最高活化能速率的步骤限制了温度不高时的循环。如果酶的总丰度受到限制，则随着更多的底物与普通酶结合，可用于催化特定反应的游离酶的量会减少。我们表明，这种游离酶丰度的变化补偿了反应系数的阿伦尼乌斯型温度依赖性。以带有多个磷酸化位点的蓝细菌蛋白KaiABC的生物钟为例，我们证明了这种温度补偿机制确实有效。具体地，如果用于磷酸化的活化能大于用于去磷酸化的活化能，则在磷酸化反应之间共享的对KaiA的竞争导致温度补偿。此外，采用一个简单的模型，我们证明了所提出的补偿机制的一般性，这不仅暗示了与生物钟的相关性，还暗示了与其他（生物）化学振荡器的相关性。

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