血红蛋白Hemoglobin

血红素是原卟啉 IX 与 Fe²⁺ 的配合物，铁与四个吡咯氮和近端组氨酸配位，第六个位置结合 O₂。氧合时铁移入卟啉平面，带动亚基间相对旋转，使血红蛋白从低亲和力的 T 态转为高亲和力的 R 态。因此一个亚基结合氧后其余亚基更易结合，氧合曲线呈 S 形（希尔系数约 2.8），既能在肺部充分载氧，又能在组织中有效释放。

Haem is protoporphyrin IX bound to Fe²⁺, with iron coordinated by four pyrrole nitrogens and the proximal histidine, and O₂ binding at the sixth site. On oxygenation the iron moves into the porphyrin plane, triggering a rotation between subunits that switches the protein from the low-affinity T state to the high-affinity R state. Binding at one subunit therefore makes binding at the others easier, giving an S-shaped oxygen-binding curve (Hill coefficient about 2.8), so haemoglobin loads fully in the lungs and unloads efficiently in tissues.

1840 年许内费尔德首次得到血红蛋白晶体。1904 年玻尔发现 CO₂ 和酸使血红蛋白释放氧（玻尔效应）。1959 年佩鲁茨用 X 射线晶体学解析了马血红蛋白结构，与解析肌红蛋白的肯德鲁共获 1962 年诺贝尔化学奖。1949 年鲍林发现镰状细胞贫血患者的血红蛋白电泳行为不同，提出“分子病”概念；1956 年英格拉姆发现病因是 β 链第 6 位谷氨酸被缬氨酸取代。

Hünefeld first obtained haemoglobin crystals in 1840. In 1904 Christian Bohr found that CO₂ and acid make haemoglobin release oxygen (the Bohr effect). In 1959 Perutz solved the structure of horse haemoglobin by X-ray crystallography and shared the 1962 Nobel Prize in Chemistry with Kendrew, who solved myoglobin. In 1949 Pauling found that sickle-cell haemoglobin behaves differently in electrophoresis and called it a molecular disease; in 1956 Ingram showed the cause is valine replacing glutamate at position 6 of the β chain.

正常成年男性血红蛋白约 130–175 g/L，女性约 115–150 g/L。CO 与血红蛋白的亲和力约为 O₂ 的 200–250 倍，因此一氧化碳中毒危害极大。亚硝酸盐等可把 Fe²⁺ 氧化为 Fe³⁺ 生成高铁血红蛋白，失去携氧能力。2,3-二磷酸甘油酸降低氧亲和力，高原适应时其浓度升高。胎儿血红蛋白（α₂γ₂）与 2,3-BPG 结合弱，氧亲和力较高，便于从母体获得氧。

Normal haemoglobin is about 130–175 g/L in adult men and 115–150 g/L in women. CO binds haemoglobin about 200–250 times more strongly than O₂, which makes carbon monoxide poisoning so dangerous. Nitrite and similar agents oxidise Fe²⁺ to Fe³⁺, forming methaemoglobin, which cannot carry oxygen. 2,3-Bisphosphoglycerate lowers oxygen affinity and rises during adaptation to altitude. Fetal haemoglobin (α₂γ₂) binds 2,3-BPG weakly and so has higher oxygen affinity, helping the fetus take oxygen from the mother.