📚 Haemoglobin: Structure, Oxygen Transport and the Bohr Effect | 血红蛋白：结构、氧气运输与玻尔效应
Haemoglobin is the iron-containing oxygen-transport metalloprotein found in red blood cells. It is responsible for picking up oxygen in the lungs and releasing it in respiring tissues, while also carrying a portion of carbon dioxide back to the lungs for excretion.
血红蛋白是红细胞中含铁的氧运输金属蛋白。它负责在肺部结合氧气，并在呼吸组织释放氧气，同时还将部分二氧化碳运回肺部排出体外。
1. Haemoglobin Structure: A Quaternary Protein | 血红蛋白结构：一种四级结构蛋白质
Haemoglobin is a globular protein with quaternary structure. In adult humans, the main form HbA consists of four polypeptide chains: two α-globin chains and two β-globin chains. Each chain is folded around one haem group, so one haemoglobin molecule contains four haem groups.
血红蛋白是一种具有四级结构的球状蛋白质。在成年人体内，主要形式 HbA 由四条多肽链组成：两条 α-珠蛋白链和两条 β-珠蛋白链。每条链围绕一个血红素基团折叠，因此一个血红蛋白分子含有四个血红素基团。
The four subunits are held together by hydrophobic interactions, hydrogen bonds and ionic bonds. This quaternary arrangement is essential for cooperative oxygen binding and allosteric regulation of oxygen affinity.
四个亚基通过疏水相互作用、氢键和离子键结合在一起。这种四级结构对于协同氧结合以及氧亲和力的别构调节至关重要。
2. The Haem Group and Iron Binding | 血红素基团与铁的结合
Each haem group contains a porphyrin ring with an iron(II) ion, Fe²⁺, at its centre. The Fe²⁺ forms six coordination bonds: four to nitrogen atoms in the porphyrin ring, one to a histidine residue of the globin chain, and one to an oxygen molecule.
每个血红素基团含有一个卟啉环，中心有一个亚铁离子 Fe²⁺。Fe²⁺ 形成六个配位键：四个与卟啉环中的氮原子相连，一个与珠蛋白链上的组氨酸残基相连，还有一个与氧分子相连。
Oxygen binds reversibly to Fe²⁺ without oxidising the iron to Fe³⁺. If oxidation occurs, methaemoglobin is formed, which cannot carry oxygen. The globin chain protects the Fe²⁺ from oxidation during normal oxygen binding.
氧气可逆地与 Fe²⁺ 结合，而不会将铁氧化成 Fe³⁺。如果发生氧化，就会形成高铁血红蛋白，无法携带氧气。珠蛋白链在正常氧结合过程中保护 Fe²⁺ 不被氧化。
3. Cooperative Oxygen Binding | 协同氧结合
Haemoglobin shows cooperative binding. The binding of the first oxygen molecule causes a conformational change in the haemoglobin molecule, making it easier for the next oxygen molecules to bind. This is described as a change from the tense (T) state to the relaxed (R) state.
血红蛋白表现出协同结合。第一个氧分子的结合引起血红蛋白分子构象变化，使后续氧分子更容易结合。这被描述为从紧张态（T 态）向松弛态（R 态）的转变。
Conversely, when one oxygen molecule is released in tissues, the molecule changes shape to make further release easier. This positive cooperativity gives the oxygen dissociation curve its characteristic S-shaped, or sigmoid, profile.
相反，当组织中的一个氧分子被释放时，分子形状发生改变，使后续氧分子更容易释放。这种正协同作用使氧解离曲线呈现特有的 S 形，即 S 型曲线。
Hb + 4O₂ ⇌ Hb(O₂)₄
4. The Oxygen Dissociation Curve | 氧解离曲线
The oxygen dissociation curve plots the percentage saturation of haemoglobin with oxygen against the partial pressure of oxygen, pO₂. At low pO₂ in respiring tissues, haemoglobin releases oxygen; at high pO₂ in the lungs, it becomes almost fully saturated.
氧解离曲线描绘血红蛋白的氧饱和度百分比与氧分压 pO₂ 之间的关系。在呼吸组织的低 pO₂ 条件下，血红蛋白释放氧气；在肺部高 pO₂ 条件下，血红蛋白几乎完全饱和。
The curve has a sigmoid shape because of cooperative binding. A steep middle portion means that a small drop in pO₂ causes a large release of oxygen, which is especially beneficial in active tissues with high oxygen demand.
由于协同结合，曲线呈 S 形。中间陡峭的部分意味着 pO₂ 的少量下降就会引起大量氧气释放，这对氧气需求高的活跃组织尤其有利。
The p₅₀ value is the pO₂ at which haemoglobin is 50% saturated. A lower p₅₀ means haemoglobin has a higher affinity for oxygen, while a higher p₅₀ means a lower affinity.
p₅₀ 值是血红蛋白达到 50% 饱和度时的 pO₂。p₅₀ 较低表示血红蛋白对氧气的亲和力较高，p₅₀ 较高则表示亲和力较低。
5. The Bohr Effect | 玻尔效应
The Bohr effect states that increased carbon dioxide concentration and increased hydrogen ion concentration, meaning lower pH, decrease haemoglobin's affinity for oxygen. This shifts the dissociation curve to the right. In actively respiring tissues, CO₂ and H⁺ are produced, so haemoglobin releases more oxygen.
玻尔效应指出，二氧化碳浓度升高和氢离子浓度升高，即 pH 降低，会降低血红蛋白对氧气的亲和力。这使解离曲线向右移动。在活跃呼吸的组织中，产生 CO₂ 和 H⁺，因此血红蛋白释放更多氧气。
CO₂ enters red blood cells and is converted by carbonic anhydrase to carbonic acid, which dissociates into H⁺ and hydrogen carbonate ions. The protons bind to haemoglobin, reducing its affinity for oxygen and promoting oxygen release.
二氧化碳进入红细胞，被碳酸酐酶转化为碳酸，碳酸再解离为 H⁺ 和碳酸氢根离子。质子与血红蛋白结合，降低其对氧气的亲和力，促进氧气释放。
CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻
The Bohr effect ensures that metabolically active tissues receive more oxygen when they need it most. In the lungs, where CO₂ is exhaled and pH rises, haemoglobin's affinity for oxygen increases again.
玻尔效应确保代谢活跃的组织在最需要时获得更多氧气。在肺部，CO₂ 被呼出，pH 升高，血红蛋白对氧气的亲和力再次增加。
6. Carbon Dioxide Transport and the Chloride Shift | 二氧化碳运输与氯转移
About 5 to 10 percent of carbon dioxide dissolves directly in plasma. About 20 to 25 percent binds to haemoglobin as carbaminohaemoglobin. About 70 percent is transported as hydrogen carbonate ions in plasma.
约 5% 至 10% 的二氧化碳直接溶解在血浆中。约 20% 至 25% 以氨基甲酸血红蛋白的形式与血红蛋白结合。约 70% 以碳酸氢根离子的形式在血浆中运输。
Inside red blood cells, carbon dioxide is converted to HCO₃⁻ and H⁺. The HCO₃⁻ moves out of the red blood cell down its concentration gradient. To maintain electrical neutrality, chloride ions, Cl⁻, enter the red blood cell. This exchange is called the chloride shift.
在红细胞内，二氧化碳被转化为 HCO₃⁻ 和 H⁺。HCO₃⁻ 沿浓度梯度移出红细胞。为了维持电中性，氯离子 Cl⁻ 进入红细胞。这种交换称为氯转移。
In the lungs, the reactions reverse. HCO₃⁻ re-enters the red blood cell, Cl⁻ leaves, and CO₂ is regenerated and exhaled. The chloride shift is therefore a reversible process linked to gas exchange.
在肺部，反应逆转。HCO₃⁻ 重新进入红细胞，Cl⁻ 离开，CO₂ 重新生成并被呼出。因此，氯转移是一个与气体交换相关的可逆过程。
7. Fetal Haemoglobin and Oxygen Affinity | 胎儿血红蛋白与氧亲和力
Fetal haemoglobin, HbF, has two α chains and two γ chains instead of the adult β chains. HbF has a higher affinity for oxygen than adult HbA, so its dissociation curve is shifted to the left.
胎儿血红蛋白 HbF 含有两条 α 链和两条 γ 链，而不是成人的 β 链。HbF 对氧气的亲和力高于成人 HbA，因此其解离曲线向左移动。
This higher affinity allows the fetus to extract oxygen from maternal blood across the placenta. At the same placental pO₂, fetal haemoglobin has a higher percentage saturation than adult haemoglobin.
这种较高的亲和力使胎儿能够通过胎盘从母体血液中摄取氧气。在相同的胎盘 pO₂ 下，胎儿血红蛋白的氧饱和度百分比高于成人血红蛋白。
After birth, the production of γ chains is replaced by β chains, and adult haemoglobin gradually becomes the dominant form. This transition is important for effective oxygen loading and unloading in postnatal life.
出生后，γ 链的合成被 β 链取代，成人血红蛋白逐渐成为主要形式。这一转变对出生后有效的氧气装载和卸载非常重要。
8. Myoglobin vs Haemoglobin | 肌红蛋白与血红蛋白比较
Myoglobin is an oxygen-binding protein found in muscle. It has a single polypeptide chain and one haem group, so it cannot show cooperative binding. Its oxygen dissociation curve is a rectangular hyperbola, not sigmoid.
肌红蛋白是肌肉中的一种氧结合蛋白。它只有一条多肽链和一个血红素基团，因此不能表现出协同结合。其氧解离曲线呈直角双曲线形，而不是 S 形。
Myoglobin has a much higher affinity for oxygen than haemoglobin. It acts as an oxygen store in muscle and releases oxygen only at very low pO₂ in actively contracting muscle tissue.
肌红蛋白对氧气的亲和力远高于血红蛋白。它在肌肉中充当氧气储存库，仅在活跃收缩的肌肉组织中 pO₂ 非常低时才释放氧气。
| Feature | Haemoglobin | Myoglobin |
|---|---|---|
| Subunits | Four polypeptide chains | One polypeptide chain |
| Haem groups | Four | One |
| Cooperativity | Yes | No |
| Curve shape | Sigmoid | Rectangular hyperbola |
| Affinity for O₂ | Lower | Higher |
| Main role | O₂ transport in blood | O₂ storage in muscle |
9. Factors Shifting the Curve: Temperature, CO₂ and 2,3-BPG | 影响曲线位移的因素：温度、二氧化碳和 2,3-BPG
The oxygen dissociation curve can shift to the right or to the left. A right shift means lower affinity for oxygen and more oxygen release. A left shift means higher affinity and less release.
氧解离曲线可以向右或向左移动。右移表示对氧气的亲和力降低，氧气释放更多。左移表示亲和力升高，释放减少。
Increased temperature, increased CO₂, increased H⁺, lower pH, and increased 2,3-bisphosphoglycerate, 2,3-BPG, all shift the curve to the right. 2,3-BPG is produced in red blood cells during glycolysis and binds to deoxyhaemoglobin, stabilising the T state.
温度升高、CO₂ 增加、H⁺ 增加、pH 降低以及 2,3-二磷酸甘油酸（2,3-BPG）增加都会使曲线向右移动。2,3-BPG 是红细胞糖酵解过程中产生的，它与脱氧血红蛋白结合，稳定 T 态。
These factors are all increased in metabolically active tissues. They ensure that haemoglobin unloads oxygen exactly where respiration is producing ATP and generating CO₂, heat and protons.
这些因素在代谢活跃的组织中都会升高。它们确保血红蛋白在呼吸产生 ATP 并生成 CO₂、热量和质子的位置准确卸载氧气。
During vigorous exercise, body temperature rises and skeletal muscles produce large amounts of CO₂ and lactic acid. The combined effect shifts the curve further to the right, enhancing oxygen delivery to working muscles.
在剧烈运动期间，体温升高，骨骼肌产生大量 CO₂ 和乳酸。综合效应使曲线进一步右移，增强向工作肌肉输送氧气的能力。
10. Carbon Monoxide Poisoning | 一氧化碳中毒
Carbon monoxide, CO, binds to the iron in haemoglobin at the same site as oxygen, but with an affinity about 250 times greater. It forms carboxyhaemoglobin, blocking oxygen transport.
一氧化碳 CO 与血红蛋白中的铁在与氧气相同的位点结合，但亲和力约高出 250 倍。它形成碳氧血红蛋白，阻断氧气运输。
CO also shifts the dissociation curve of the remaining haem groups to the left. This means that the small amount of oxygen that does bind is released less readily to the tissues. As a result, carbon monoxide poisoning can be rapidly fatal even at relatively low concentrations.
CO 还会使剩余血红素基团的解离曲线向左移动。这意味着已经结合的少量氧气更不容易释放给组织。因此，即使在相对较低的浓度下，一氧化碳中毒也可能迅速致命。
Treatment usually involves giving pure oxygen or hyperbaric oxygen, which increases pO₂ and helps displace CO from haemoglobin. This example shows how competitive inhibition at the oxygen-binding site disrupts normal transport.
治疗通常包括给予纯氧或高压氧，从而增加 pO₂ 并帮助将 CO 从血红蛋白中置换出来。这一例子说明氧结合位点的竞争性抑制如何破坏正常运输。
11. Exam Tips and Common Misconceptions | 考试技巧与常见误区
A common error is saying haemoglobin has four haem groups but failing to link this to four oxygen molecules. Each of the four subunits carries one haem group, so one haemoglobin molecule can bind up to four O₂ molecules.
一个常见错误是提到血红蛋白有四个血红素基团，但没有将其与四个氧分子联系起来。四个亚基各携带一个血红素基团，因此一个血红蛋白分子最多可以结合四个 O₂ 分子。
Another misconception is that the Bohr effect refers only to pH. You should link it to CO₂ and H⁺ produced by respiring tissues, and explain how protons binding to haemoglobin reduce its affinity for oxygen.
另一个误区是认为玻尔效应仅与 pH 有关。你应当将其与呼吸组织产生的 CO₂ 和 H⁺ 联系起来，并解释质子与血红蛋白结合如何降低其对氧气的亲和力。
Use precise terms such as cooperative binding, allosteric change, affinity, conformational change, and saturation when explaining curve shifts. Avoid vague phrases like "the curve moves" without saying which direction and why.
在解释曲线位移时，应使用准确术语，如协同结合、别构变化、亲和力、构象变化和饱和度。避免使用“曲线移动”等模糊说法，而不说明方向和原因。
When comparing HbA and HbF, always state that fetal haemoglobin has a higher affinity for oxygen and a left-shifted curve. Then explain the advantage in terms of oxygen transfer across the placenta.
在比较 HbA 和 HbF 时，一定要说明胎儿血红蛋白对氧气的亲和力更高，曲线左移。然后从氧气跨胎盘转运的角度解释其优势。
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