The chemist mocked in 1825 for weighing a molecule too big to believe
Johann Friedrich Engelhart noticed that hemoglobin carries iron in a fixed ratio across species, and from iron's atomic mass he worked out a molecular weight in multiples of 16,000. Colleagues laughed at the idea of anything that large. A century later, in 1925, Gilbert Adair measured it again and proved him right.
Engelhart's figure was the first time anyone had calculated the mass of a protein. We now know each hemoglobin carries four iron atoms, one inside each of its four subunits. Every subunit is a folded globin chain wrapped around a heme group, which is where the name comes from, and each iron can grip one oxygen molecule. The four units sit in a rough tetrahedron, and their cooperation lets the whole assembly load and unload oxygen efficiently.
The payoff is enormous. A gram of hemoglobin binds 1.34 millilitres of oxygen, lifting blood's carrying capacity about seventy times above what plasma could dissolve alone. The protein makes up roughly 96 percent of a red cell's dry weight, and a healthy person has 12 to 20 grams in every 100 millilitres of blood. It also hauls away a fifth to a quarter of the body's carbon dioxide and ferries nitric oxide, a signalling molecule.
Other milestones followed. Hunefeld described its oxygen-carrying role in 1840, Otto Funke grew hemoglobin crystals in 1851, and Felix Hoppe-Seyler showed that oxygen binding is reversible. In 1959 Max Perutz solved its structure by X-ray crystallography, sharing the 1962 Nobel Prize in Chemistry with John Kendrew. Sickle-cell disease, caused by a hemoglobin mutation, became the first human illness understood at the molecular level.
Evolution has tuned the molecule everywhere. Human and chimpanzee versions are identical, while gorillas differ by one amino acid per chain. Mammoth hemoglobin worked at lower temperatures, Andean hummingbirds carry mutations that grab oxygen in thin air, and highland deer mice differ from lowland cousins mainly in these genes. Most Antarctic icefish have abandoned hemoglobin entirely, the lone vertebrate family without it.
Source: Hemoglobin
