📚 Haemoglobin: Structure and Oxygen-Binding Properties | 血红蛋白的结构与氧结合特性
Haemoglobin is a globular protein found in red blood cells, responsible for the transport of oxygen from the lungs to respiring tissues. Its unique quaternary structure and cooperative oxygen-binding mechanism make it perfectly adapted to its physiological role. This article provides a comprehensive revision guide for CIE A-Level Biology, covering the structural features, oxygen dissociation curves, and the factors that influence oxygen affinity.
血红蛋白是一种存在于红细胞中的球状蛋白质，负责将氧气从肺部运输至进行呼吸作用的组织。其独特的四级结构和协同性氧结合机制，使其完美适应这一生理功能。本文为CIE A-Level生物学的备考指南，系统讲解血红蛋白的结构特征、氧解离曲线以及影响氧亲和力的各种因素。
1. Location and General Function | 位置与总体功能
In mammals, haemoglobin is contained within red blood cells (erythrocytes). This intracellular localisation offers several advantages: it prevents the protein from increasing blood viscosity and causing osmotic problems, and it allows the blood plasma to remain a free-flowing transport medium for other substances such as dissolved gases, hormones and nutrients.
在哺乳动物中，血红蛋白存在于红细胞内。这种胞内定位具有若干优势：可防止该蛋白质增加血液粘稠度并引发渗透压问题，同时使血浆保持为其他物质（如溶解气体、激素和营养物质）自由流动的运输介质。
The primary role of haemoglobin is to bind oxygen at the respiratory surface (the alveoli in humans) and release it at the respiring tissues. However, haemoglobin also plays a minor role in carbon dioxide transport: about 10-20% of carbon dioxide in the blood is transported bound to haemoglobin, forming carbaminohaemoglobin.
血红蛋白的主要作用是在呼吸表面（人的肺泡处）结合氧气，并在呼吸组织中释放。此外，血红蛋白在二氧化碳运输中也起次要作用：血液中约10-20%的二氧化碳与血红蛋白结合运输，形成氨甲酰血红蛋白。
2. Quaternary Structure of Haemoglobin | 血红蛋白的四级结构
Haemoglobin is a conjugated protein with a quaternary structure. It consists of four polypeptide chains — two alpha (α) globin chains and two beta (β) globin chains — held together by hydrophobic interactions, hydrogen bonds and ionic bonds. Each polypeptide chain is associated with a non-protein prosthetic group known as a haem group.
血红蛋白是一种具有四级结构的结合蛋白。它由四条多肽链组成——两条α珠蛋白链和两条β珠蛋白链——通过疏水相互作用、氢键和离子键结合在一起。每条多肽链与一个称为血红素基团的非蛋白质辅基相连。
The haem group contains an iron(II) ion (Fe²⁺) at its centre, which is coordinated by four nitrogen atoms of a porphyrin ring. This Fe²⁺ ion is the actual site where one oxygen molecule binds reversibly. Since each haemoglobin molecule has four haem groups, it can carry up to four oxygen molecules simultaneously.
血红素基团中心含有一个亚铁离子（Fe²⁺），该离子与卟啉环的四个氮原子配位。这个Fe²⁺离子是氧气分子可逆结合的实际位点。由于每个血红蛋白分子含有四个血红素基团，因此它最多可同时携带四个氧气分子。
- Two α-chains: each contains 141 amino acid residues | 两条α链：每条含141个氨基酸残基
- Two β-chains: each contains 146 amino acid residues | 两条β链：每条含146个氨基酸残基
- Haem group: C₃₄H₃₂N₄Fe, containing a central Fe²⁺ ion | 血红素基团：C₃₄H₃₂N₄Fe，含中心Fe²⁺离子
3. The Haem Group and Iron(II) Ion | 血红素基团与亚铁离子
The haem group is planar in structure, consisting of a porphyrin ring with a central iron ion. The iron ion forms four coordinate bonds with the nitrogen atoms of the porphyrin ring. A fifth coordinate bond links the iron to a histidine residue (proximal histidine, His F8) of the globin chain, anchoring the haem group in place within the protein. The sixth coordination position is available for oxygen binding.
血红素基团为平面结构，由卟啉环和中心铁离子组成。铁离子与卟啉环的四个氮原子形成四个配位键。第五个配位键将铁离子与珠蛋白链上的一个组氨酸残基（近端组氨酸，His F8）连接，将血红素基团锚定在蛋白质内部。第六个配位位置可用于结合氧气。
It is crucial that the iron remains in the Fe²⁺ (ferrous) state. If the iron is oxidised to Fe³⁺ (ferric), the resulting molecule is methaemoglobin, which cannot bind oxygen effectively. This oxidation can be triggered by certain drugs or environmental toxins. The hydrophobic pocket surrounding the haem group protects the Fe²⁺ from oxidation and prevents the formation of toxic free radicals.
关键在于铁必须保持Fe²⁺（亚铁）状态。如果铁被氧化为Fe³⁺（高铁），所得分子称为高铁血红蛋白，无法有效结合氧气。某些药物或环境毒素可诱使这种氧化反应。血红素基团周围的疏水口袋保护Fe²⁺不被氧化，并防止有毒自由基的形成。
O₂ + Hb(Fe²⁺) ⇌ HbO₂ (oxyhaemoglobin, Fe²⁺-O₂)
4. Cooperative Binding of Oxygen | 氧的协同结合
The most remarkable feature of haemoglobin is its cooperative binding of oxygen. The binding of the first oxygen molecule to one haem group induces a conformational change in the protein — from the tense (T) state to the relaxed (R) state — which increases the oxygen affinity of the remaining three haem groups. In other words, after the first oxygen binds, subsequent oxygen molecules bind more readily.
血红蛋白最显著的特征是其对氧气的协同结合。第一个氧气分子与一个血红素基团结合后，会引起蛋白质的构象变化——从紧张态（T态）转变为松弛态（R态）——从而增加其余三个血红素基团对氧的亲和力。换言之，在第一个氧结合之后，后续氧分子更易结合。
This cooperativity gives haemoglobin a sigmoidal (S-shaped) oxygen dissociation curve. Without cooperativity, the curve would be hyperbolic, similar to that of myoglobin. The sigmoidal shape is physiologically significant: it allows haemoglobin to load oxygen efficiently at high partial pressures (in the lungs) and unload oxygen efficiently at low partial pressures (in respiring tissues).
这种协同性使血红蛋白具有S形（乙状）氧解离曲线。如果没有协同性，曲线将是双曲线形，类似于肌红蛋白的曲线。S形曲线具有重要的生理意义：它使血红蛋白在高氧分压（肺部）下高效装载氧气，在低氧分压（呼吸组织中）下高效卸载氧气。
5. The Oxygen Dissociation Curve | 氧解离曲线
The oxygen dissociation curve plots the percentage saturation of haemoglobin against the partial pressure of oxygen (pO₂), measured in kilopascals (kPa). At a pO₂ of approximately 12-13 kPa (the partial pressure in the alveoli), haemoglobin reaches about 97-98% saturation. At a pO₂ of about 4 kPa (the typical partial pressure in respiring tissues), saturation drops to roughly 70%.
氧解离曲线以血红蛋白的百分饱和度对氧分压（pO₂，单位kPa）作图。在肺泡中氧分压约为12-13 kPa时，血红蛋白饱和度达到约97-98%。在呼吸组织中典型氧分压约4 kPa时，饱和度下降至约70%。
The difference in saturation between the lungs and the tissues — approximately 25-30% — represents the oxygen actually delivered to the tissues under resting conditions. This value is known as the oxygen unloading capacity, and it may increase significantly during exercise when tissue pO₂ falls even lower.
肺与组织之间的饱和度差——约25-30%——代表静息条件下实际释放给组织的氧气量。该值称为氧卸载能力，运动时组织pO₂进一步下降，此值可能显著增加。
| Condition | 条件 | pO₂ (kPa) | 氧分压 | % Saturation | 饱和度 |
| Alveoli | 肺泡 | 12-13 | 97-98% |
| Resting tissues | 静息组织 | 4-5 | 70-75% |
| Active tissues | 活跃组织 | 1-2 | 20-30% |
6. The Bohr Effect: Effect of pH and CO₂ | 波尔效应：pH与CO₂的影响
The oxygen affinity of haemoglobin is significantly affected by the partial pressure of carbon dioxide (pCO₂) and the pH of the surrounding environment. An increase in pCO₂ or a decrease in pH (increased acidity) causes haemoglobin to release oxygen more readily. This is known as the Bohr effect. In actively respiring tissues, high CO₂ production leads to the formation of carbonic acid (H₂CO₃), which lowers pH and promotes the release of oxygen.
血红蛋白的氧亲和力受周围环境的二氧化碳分压（pCO₂）和pH的显著影响。pCO₂升高或pH降低（酸性增强）会使血红蛋白更易释放氧气。这称为波尔效应。在活跃呼吸的组织中，大量CO₂生成导致碳酸（H₂CO₃）的形成，从而降低pH并促进氧气的释放。
The mechanism involves the stabilisation of the T-state. Hydrogen ions (H⁺) and CO₂ bind to specific amino acid residues in the globin chains — particularly the N-terminal amino groups and histidine residues — forming salt bridges that stabilise the low-affinity T-state. This shifts the oxygen dissociation curve to the right, a response known as the right shift of the curve.
该机制涉及T态的稳定化。氢离子（H⁺）和CO₂与珠蛋白链中的特定氨基酸残基结合——特别是N-末端氨基和组氨酸残基——形成稳定低亲和力T态的盐桥。这使氧解离曲线右移，这种响应称为曲线右移。
CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻
A rightward shift of the oxygen dissociation curve at higher CO₂/lower pH means that at any given pO₂, haemoglobin holds onto oxygen less tightly. The opposite is true in the lungs: as CO₂ is released, pH rises, the curve shifts left, and haemoglobin’s affinity for oxygen increases, facilitating oxygen loading. The Bohr effect therefore enhances oxygen delivery precisely where and when it is most needed — in metabolically active tissues.
在较高CO₂/较低pH下，氧解离曲线右移意味着在任一给定pO₂处，血红蛋白对氧的结合力减弱。在肺部则相反：CO₂被释放后，pH升高，曲线左移，血红蛋白对氧的亲和力增加，从而促进氧的装载。因此，波尔效应恰好能促进氧气在代谢活跃组织中准确、适时的释放。
7. Effect of Temperature | 温度的影响
Temperature also affects haemoglobin’s oxygen-binding behaviour. Increased temperature causes a right shift of the oxygen dissociation curve, meaning that haemoglobin unloads more oxygen to the tissues. This is because higher temperatures provide more kinetic energy, increasing molecular vibrations and destabilising the hydrogen bonds and ionic interactions that hold the protein in its relaxed R-state.
温度同样影响血红蛋白的氧结合行为。温度升高导致氧解离曲线右移，意味着血红蛋白向组织释放更多氧气。这是因为较高的温度提供更多动能，增强分子振动，从而破坏使蛋白质维持松弛R态的氢键和离子相互作用。
This effect is particularly important during vigorous exercise. Active skeletal muscles generate substantial heat, raising local tissue temperature. The combination of elevated temperature, high CO₂ and low pH in exercising muscle creates a powerful synergistic effect that maximises oxygen unloading to the muscle fibres, supporting the increased rate of aerobic respiration required for ATP production.
该效应在剧烈运动中尤为重要。活跃的骨骼肌产生大量热量，使局部组织温度升高。运动肌肉中温度升高、CO₂升高和pH降低的组合产生了强大的协同效应，最大限度地增加了向肌纤维的氧卸载，支持了ATP生产所需的有氧呼吸速率增加。
8. Effect of 2,3-Bisphosphoglycerate (2,3-BPG) | 2,3-二磷酸甘油酸的影响
2,3-Bisphosphoglycerate (2,3-BPG), formerly known as 2,3-diphosphoglycerate, is a metabolite produced in red blood cells during glycolysis. It binds to the central cavity of the deoxygenated (T-state) haemoglobin tetramer, forming ionic bonds with the β-chains. This binding stabilises the T-state and reduces the oxygen affinity of haemoglobin, shifting the oxygen dissociation curve to the right.
2,3-二磷酸甘油酸（2,3-BPG），旧称2,3-二磷酸甘油酸酯，是红细胞在糖酵解过程中产生的代谢物。它与脱氧（T态）血红蛋白四聚体的中央空腔结合，与β链形成离子键。这种结合使T态稳定化并降低血红蛋白的氧亲和力，使氧解离曲线右移。
The concentration of 2,3-BPG increases under conditions of chronic hypoxia — such as at high altitude, in chronic lung disease or in severe anaemia. This adaptive response ensures that tissues still receive adequate oxygen despite lower ambient pO₂ or reduced haemoglobin levels. Conversely, stored blood used for transfusion has reduced 2,3-BPG levels over time, temporarily increasing its oxygen affinity; this is why fresh blood is preferred for critically ill patients.
在慢性缺氧条件下——如高海拔、慢性肺病或严重贫血——2,3-BPG浓度升高。这种适应性反应确保组织在环境pO₂较低或血红蛋白减少的情况下仍能获得足够的氧气。相反，储存的输血用血中2,3-BPG水平随时间下降，其氧亲和力会暂时升高；这也是危重病人优先使用新鲜血液的原因。
9. Haemoglobin Types in Development | 发育过程中的血红蛋白类型
During human development, different globin genes are expressed at different stages. Embryonic haemoglobin (Gower 1 and Gower 2) contains zeta (ζ) and epsilon (ε) chains. Fetal haemoglobin (HbF, α₂γ₂) replaces embryonic haemoglobin from the second trimester. HbF has a higher oxygen affinity than adult haemoglobin (HbA, α₂β₂) because it binds 2,3-BPG less strongly — its γ-chains lack some of the positively charged residues present in the β-chains of adult haemoglobin.
在人类发育过程中，不同的珠蛋白基因在不同阶段表达。胚胎血红蛋白（Gower 1和Gower 2）含有ζ链和ε链。胎儿血红蛋白（HbF, α₂γ₂）在妊娠中期取代胚胎血红蛋白。HbF对氧的亲和力高于成人血红蛋白（HbA, α₂β₂），原因是它与2,3-BPG的结合较弱——其γ链缺少成人血红蛋白β链中的一些正电荷残基。
This higher oxygen affinity of fetal haemoglobin is essential for the transfer of oxygen from the maternal blood across the placenta to the fetal circulation. When the mother’s haemoglobin releases oxygen in the placental capillaries due to the Bohr effect, the fetal haemoglobin, with its greater affinity, competes successfully for oxygen molecules and carries them to the developing fetal tissues.
胎儿血红蛋白较高的氧亲和力对氧气从母体血液经胎盘转移至胎儿循环至关重要。当母体血红蛋白因波尔效应在胎盘毛细血管释放氧气时，具有更高亲和力的胎儿血红蛋白能成功竞争到氧分子，并将其运送到发育中的胎儿组织。
10. Haemoglobinopathies: Sickle Cell Anaemia | 血红蛋白病：镰状细胞贫血
Sickle cell anaemia is a genetic disorder caused by a single point mutation in the β-globin gene. The sixth amino acid of the β-chain, glutamic acid (a polar, negatively charged residue), is replaced by valine (a non-polar, hydrophobic residue). This single amino acid substitution — a change of only one nucleotide in the DNA (GAG → GTG) — has profound consequences for the behaviour of haemoglobin.
镰状细胞贫血是由β珠蛋白基因单一碱基点突变引起的遗传病。β链第六位氨基酸——谷氨酸（极性、带负电荷的残基）被缬氨酸（非极性、疏水残基）替代。这种单个氨基酸替换——DNA中仅有一个核苷酸的变化（GAG→GTG）——对血红蛋白的行为产生深远影响。
In its deoxygenated state, the mutant haemoglobin (HbS) polymerises into long rod-like fibres, causing red blood cells to assume a characteristic sickle or crescent shape. These sickled cells are rigid and fragile; they can block small blood vessels, causing painful crises, and they are removed rapidly from circulation, leading to chronic haemolytic anaemia. Carriers of the sickle cell trait (heterozygotes) show mild symptoms and have a survival advantage against malaria in endemic regions.
在脱氧状态下，突变血红蛋白（HbS）聚合成细长的纤维杆状，使红细胞呈现特征性的镰刀状或新月状。这些镰状细胞僵硬而脆弱，可能堵塞小血管，引起疼痛危象，并且很快被从循环中清除，导致慢性溶血性贫血。镰状细胞性状携带者（杂合子）症状较轻，且在疟疾流行区具有抗疟疾的生存优势。
11. Comparing Haemoglobin with Myoglobin | 血红蛋白与肌红蛋白的比较
Myoglobin is a monomeric oxygen-binding protein found in skeletal and cardiac muscle tissue. It consists of a single polypeptide chain of 153 amino acid residues, folding into eight α-helices around a single haem group. As a monomer without cooperative binding, myoglobin has a hyperbolic oxygen dissociation curve and a much higher oxygen affinity than haemoglobin.
肌红蛋白是存在于骨骼肌和心肌组织中的单体氧结合蛋白。它由单条153个氨基酸残基的多肽链组成，绕单一血红素基团折叠成八个α螺旋。由于是单体且无协同结合，肌红蛋白具有双曲线型氧解离曲线，其对氧的亲和力远高于血红蛋白。
Myoglobin serves as an oxygen reservoir within muscle fibres, storing oxygen supplied by the blood and releasing it during periods of intense exercise when muscle pO₂ becomes very low. It also facilitates the diffusion of oxygen from the blood to the mitochondria — the site of oxidative phosphorylation. The P₅₀ value (the pO₂ at which the protein is 50% saturated) for myoglobin is approximately 1-2 kPa, whereas for haemoglobin it is roughly 3.5-4 kPa under standard conditions.
肌红蛋白充当肌纤维内的氧储存库，储存血液供应的氧气，并在剧烈运动期间肌肉pO₂变得很低时将其释放。它还促进氧气从血液到线粒体（氧化磷酸化的位点）的扩散。肌红蛋白的P₅₀值（使蛋白质达到50%饱和时的pO₂）约为1-2 kPa，而血红蛋白在标准条件下约为3.5-4 kPa。
| Property | 特性 | Haemoglobin | 血红蛋白 | Myoglobin | 肌红蛋白 |
| Structure | 结构 | Tetramer (4 subunits) | 四聚体（4个亚基） | Monomer (1 subunit) | 单体（1个亚基） |
| Cooperative binding | 协同结合 | Yes | 有 | No | 无 |
| Curve shape | 曲线形状 | Sigmoidal | S形 | Hyperbolic | 双曲线 |
| Oxygen affinity | 氧亲和力 | Moderate | 中等 | High | 高 |
| Location | 位置 | Red blood cells | 红细胞 | Muscle tissue | 肌肉组织 |
12. Exam-Focused Summary | 考点总结
For CIE A-Level Biology examinations, the key points to remember about haemoglobin are: the quaternary structure with two α- and two β-globin chains; the role of the haem group with Fe²⁺ in oxygen binding; the cooperative nature of oxygen binding producing a sigmoidal dissociation curve; and the effects of pCO₂, pH and temperature on oxygen affinity, which produce a right or left shift of the curve. Be prepared to draw and interpret oxygen dissociation curves, and to explain the physiological significance of the Bohr effect in different tissues.
对于CIE A-Level生物考试，关于血红蛋白需要记住的关键要点是：具有两条α链和两条β链的四级结构；血红素基团中Fe²⁺在氧结合中的作用；氧结合的协同性产生的S形解离曲线；以及pCO₂、pH和温度对氧亲和力的影响，导致曲线右移或左移。考生应准备好绘制和解读氧解离曲线，并解释波尔效应在不同组织中的生理意义。
Common exam questions may ask you to compare the oxygen dissociation curves of haemoglobin and myoglobin, to explain how fetal haemoglobin differs from adult haemoglobin, or to relate the structure of haemoglobin to its function in oxygen transport. Remember that the sigmoidal curve is a direct consequence of cooperative binding, and that the Bohr effect optimises oxygen delivery at the tissue level while maintaining efficient loading at the respiratory surface.
常见考题可能要求你比较血红蛋白和肌红蛋白的氧解离曲线，解释胎儿血红蛋白如何不同于成人血红蛋白，或将血红蛋白的结构与其氧运输功能联系起来。记住S形曲线是协同结合的直接结果，而波尔效应在组织水平优化氧释放，同时保持呼吸表面的高效装载。
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