THERMODYNAMIC STUDIES OF ELECTRON AND PROTON AFFINITIES OF CYTOCHROMES

细胞色素的电子和质子亲和力的热力学研究

• 批准号: 3966521
• 负责人: R W HENDLER
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3966521
• 关键词: Escherichia coli; bioenergetics; biomedical automation; cell biology; cell membrane; cellular respiration; cytochrome b; cytochrome oxidase; cytochromes; electron transport; heart cell; hydrogen transport; liver cells; mathematical model; mitochondria; oxidation reduction reaction; potentiometry; thermodynamics

Many theoretical issues were raised by our newer findings on the spectral and thermodynamic characterization of cytochrome aa3. Our finding that CO did not raise the Em of cytochrome a3 is contrary to theory for a case where a ligand binds more strongly to the reduced member of a redox couple. We proposed that protons are second ligands that bind more strongly to the oxidized member of the CO-liganded couple. A theoretical paper published early this year using other considerations reached the opposite conclusion. In an intensive theoretical examination of cooperativity for a system involving three ligands (electron, proton, and CO), we were able to explain how the later results do not rule out cooperative interactions involving protons and how multi-ligand interactions could be effectively utilized for a redox-drive Bohr-type proton pump. Other of our newer findings posed additional theoretical questions. We concluded that the redox potential of cytochrome a3 was under the control of the redox state of other centers in the molecule. We found that lowering the voltage first oxidized cytochrome a3 and then reduced it. Existing theory does not account for these phenomena. Cytochrome oxidase can theoretically possess from 4 to 13 redox centers. The Em of any center may be cooperatively affected by any combination of electrons in the other centers. We have started a quantitative theoretical consideration of the expected effects of redox interactions in a variety of possible models based on cytochrome oxidase. Preliminary results indicate that redox cooperativity can account for our newer results. A research collaboration was initiated with the laboratory of Britton Chance. Our newer intensive analytical techniques, in equilibrium studies, revealed specific spectral components and interactions. We hope to use the same analytical technique in kinetic studies coupled with our newer characterizations of the components to study the mechanism of cytochrome oxidase activity. Preliminary results do show the same kinds of spectra we had encountered in our work.

我们在光谱上的新发现提出了许多理论问题 和细胞色素AA3的热力学表征。 我们的发现 没有提出细胞色素A3的EM与理论相反 其中配体与氧化还原的减少成员更强烈结合 夫妻。 我们提出质子是第二配体，其结合更多 强烈地是共同配合夫妇的氧化成员。 理论 本年初发表的论文使用其他注意事项达到了 相反的结论。 在深入的理论考试中 涉及三个配体的系统（电子，质子和 co），我们能够解释以后的结果如何不排除 涉及质子的合作相互作用以及如何多配体 可以有效地用于氧化还原驱动的BOHR型相互作用 质子泵。 我们的其他新发现提出了其他理论 问题。 我们得出的结论是，细胞色素A3的氧化还原潜力是 在分子其他中心的氧化还原状态下。 我们 发现降低电压首先氧化了细胞色素A3，然后 减少了它。 现有理论不能解释这些现象。 从理论上讲，细胞色素氧化酶可以从4到13个氧化还原中心拥有。 任何中心的EM可能会受到任何组合的合作影响 其他中心的电子。 我们已经开始定量理论 考虑多种氧化还原相互作用的预期影响多种 可能基于细胞色素氧化酶的模型。 初步结果表明 这种氧化还原的合作性可以解释我们的新结果。 研究 与布里顿机会实验室启动了合作。 我们的 在平衡研究中，较新的密集分析技术显示 特定的光谱成分和相互作用。 我们希望使用同样的 动力学研究中的分析技术与我们的新 研究细胞色素机理的成分的表征 氧化酶活性。 初步结果确实显示了我们的类型的光谱 在我们的工作中遇到了。