Quantum chemistry reveals thermodynamic principles of redox biochemistry.
Quantum chemistry reveals thermodynamic principles of redox biochemistry.
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DOI：
10.1371/journal.pcbi.1006471
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发表时间：
2018-10
影响因子：
4.3
通讯作者：
Bar-Even A
中科院分区：
文献类型：
--
作者：
Jinich A;Flamholz A;Ren H;Kim SJ;Sanchez-Lengeling B;Cotton CAR;Noor E;Aspuru-Guzik A;Bar-Even A
热力学决定了新陈代谢的结构和功能。氧化还原反应驱动细胞能量和物质流动。因此，准确量化氧化还原反应的热力学应该揭示塑造细胞代谢的设计原则。然而，只有很少的氧化还原电位被测量，而且大多数实验设置不一致。在这里，我们开发了一种量子化学方法来计算生化反应的氧化还原电位，并证明我们的方法以无与伦比的准确性预测实验测量的电位。然后，我们计算了生物化学相关化合物产生的所有氧化还原对的电位，并强调了氧化还原生物化学的基本趋势。我们进一步解决了为什么NAD/NADP被用作主要电子载体的问题，展示了它们的生理电位范围如何符合中枢代谢反应和最小化活性羰基的浓度。量子化学的使用可以通过快速准确地计算热力学值来彻底改变我们对生化现象的理解。氧化还原反应定义了生命可以存在的能量限制。然而，还原电位的测量是稀缺和不标准化的，目前的预测方法没有达到预期的准确性和覆盖范围。在这里，我们利用量子化学工具来实现还原电位的高通量预测，具有无与伦比的准确性。我们计算了所有氧化还原对的还原电位，可以产生使用已知的生化化合物。这个高分辨率的数据集使我们能够揭示新陈代谢的全球趋势，包括氧化还原酶组之间和组内的差异。我们进一步证明，NAD(P)的氧化还原电位最优地满足两个约束条件：可逆地还原和氧化中心代谢中的绝大多数氧化还原反应，同时保持活性羰基中间体的浓度得到控制。
Thermodynamics dictates the structure and function of metabolism. Redox reactions drive cellular energy and material flow. Hence, accurately quantifying the thermodynamics of redox reactions should reveal design principles that shape cellular metabolism. However, only few redox potentials have been measured, and mostly with inconsistent experimental setups. Here, we develop a quantum chemistry approach to calculate redox potentials of biochemical reactions and demonstrate our method predicts experimentally measured potentials with unparalleled accuracy. We then calculate the potentials of all redox pairs that can be generated from biochemically relevant compounds and highlight fundamental trends in redox biochemistry. We further address the question of why NAD/NADP are used as primary electron carriers, demonstrating how their physiological potential range fits the reactions of central metabolism and minimizes the concentration of reactive carbonyls. The use of quantum chemistry can revolutionize our understanding of biochemical phenomena by enabling fast and accurate calculation of thermodynamic values. Redox reactions define the energetic constraints within which life can exist. However, measurements of reduction potentials are scarce and unstandardized, and current prediction methods fall short of desired accuracy and coverage. Here, we harness quantum chemistry tools to enable the high-throughput prediction of reduction potentials with unparalleled accuracy. We calculate the reduction potentials of all redox pairs that can be generated using known biochemical compounds. This high-resolution dataset enables us to uncover global trends in metabolism, including the differences between and within oxidoreductase groups. We further demonstrate that the redox potential of NAD(P) optimally satisfies two constraints: reversibly reducing and oxidizing the vast majority of redox reactions in central metabolism while keeping the concentration of reactive carbonyl intermediates in check.
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影响因子：
4.4
作者：
Becke, Axel D.;Johnson, Erin R.
通讯作者：
Johnson, Erin R.
影响因子：
2.1
作者：
DEWAR, MJS;TRINAJST.N
通讯作者：
TRINAJST.N
影响因子：
9.9
作者：
通讯作者：
--
影响因子：
4.3
作者：
Bar-Even A;Noor E;Flamholz A;Buescher JM;Milo R
通讯作者：
Milo R
DOI：
10.1073/pnas.0907176107
发表时间：
2010-05-11
影响因子：
11.1
作者：
Bar-Even, Arren;Noor, Elad;Milo, Ron
通讯作者：
Milo, Ron