THE PROBLEM OF THE HEME INTERACTIONS IN HEMOGLOBIN AND THE BASIS OF THE BOHR EFFECT
THE PROBLEM OF THE HEME INTERACTIONS IN HEMOGLOBIN AND THE BASIS OF THE BOHR EFFECT
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DOI：
10.1002/pol.1951.120070506
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发表时间：
1951-01-01
影响因子：
3.4
通讯作者：
ALLEN, DW
中科院分区：
文献类型：
--
作者：
WYMAN, J;ALLEN, DW
在本文中，我们已经提出，血红蛋白的血红素之间的相互作用主要是由于熵效应与作为一个整体的分子的构型变化。在血红蛋白中，四个血红素似乎出现在巴黎中，同一对血红素中的成员之间的相互作用估计相当于每度12卡路里或更多的熵效应，这与当等于血红蛋白一半重量的橡胶被拉伸到其初始长度的两倍到三倍时发生的熵变化大致相同。这种熵变可以解释在血红蛋白被尿素一分为二的氧和氧化平衡中观察到的n = 1.9的值。这里提出的构型假说可以立即解释完整血红蛋白的氧、一氧化碳和氧化平衡之间的密切相似性，因为X射线研究表明，伴随所有三种反应的是相同的构型变化。它也可以解释血红蛋白和氧合血红蛋白之间溶解度的差异，以及其他一些问题。本文介绍了镰状细胞贫血血红蛋白氧合作用的一些新数据，并结合这一假说进行了讨论，进一步提出玻尔效应可能不是由Coryell和Pauling提出的血红素珠蛋白键的键型变化引起的，而是由于血红蛋白分子整体构型的变化而引起的某些酸性基团的位置和环境的变化。这就解释了玻尔效应对于氧化、氧合、与一氧化碳结合以及其他事物的本质同一性。最后提出，在血红蛋白中假设的那种熵效应可能在更普遍的酶激活底物中起作用。正如我们已经指出的，本文提出的建议具有高度的推测性，其价值在很大程度上取决于它们在多大程度上指向新的实验。在众多问题中，有以下几个问题：只有一层多肽链的肌红蛋白在氧化时是否发生构型变化？当血红蛋白与各种试剂联合收割机结合，而这些试剂与分子中的特定基团发生反应时，相互作用和玻尔效应会发生什么变化？当血红蛋白分子与氧结合并改变形状时，其偶极矩是否发生了显著变化？这些问题和其他问题如果得到回答，将与本文件提出的建议高度相关。
In this paper we have suggested that the interaction between the hemes of hemoglobin is due primarily to entropy effects associated with configurational changes in the molecule as a whole. In hemoglobin the four hemes appear to occur in paris, and the estimated interaction between members of the same pair would correspond to an entropy effect of 12 calories per degree or more, which is roughly the same as the entropy change which occurs when a mass of rubber equal to the half weight of hemoglobin is stretched to between twice and three times its initial length. Such an entropy change would account for the value ofn= 1.9 observed in the oxygen and oxidation equilibria of hemoglobin split in halves by urea. The configurational hypothesis here proposed would at once explain the close similarity between the oxygen, carbon monoxide, and oxidation equilibria of intact hemoglobin, for x‐ray studies indicate that the same configurational changes accompany all three reactions. It would also account for the difference of solubility between hemoglobin and oxyhemoglobin, as well as a number of other matters. Some new data on the oxygenation of sickle‐cell anemia hemoglobin are presented and discussed in connection with the hypothesis.The further suggestion is made that the Bohr effect may be due, not to changes of bond type in the heme globin linkage as proposed by Coryell and Pauling, but to changes in the position and environment of certain acid groups resulting from changes in the configuration of the hemoglobin molecular as a whole. This would explain the essential identity of the Bohr effect for oxidation, oxygenation, and combination with carbon monoxide, as well as other things.It is finally suggested that the kind of entropy effect postulated in hemoglobin may play a role in the activation of substrates by enzymes more generally.As we have pointed out, the suggestions made in this paper are highly speculative and their value will depend largely on the extent to which they point to new experiments. Among many questions which arise are these: Is there any configurational change which occurs in myoglobin, with only a single layer of polypeptide chain, when it is oxygenated? What happens to the interaction and the Bohr effect when hemoglobin is caused to combine with a variety of reagents which react with specific groups in the molecule? Is there any significant change in the dipole moment of the hemoglobin molecule when it combines with oxygen and changes shape? These and other questions, if they were answered, would be highly pertinent to the suggestions presented in this paper.