Hemoglobin is a complex protein found within red blood cells. Its primary function is to serve as the body’s oxygen transport system, picking up oxygen from the lungs and carrying it through the bloodstream to tissues for metabolism. This protein also transports a portion of the carbon dioxide produced by tissues back to the lungs for exhalation.
Hemoglobin’s Quaternary Structure
A single molecule of adult human hemoglobin (HbA) is a heterotetramer, built from four separate protein chains, or subunits, assembled together. This arrangement of multiple polypeptide chains is known as the quaternary structure. Adult hemoglobin typically consists of two identical alpha (\(\alpha\)) chains and two identical beta (\(\beta\)) chains, often denoted as \(\alpha_2\beta_2\).
Each individual protein chain is tightly associated with one heme group. Since the entire hemoglobin molecule is composed of four subunits, it inherently contains four heme groups. This means that one complete hemoglobin molecule has four distinct sites capable of binding oxygen. The four polypeptide subunits are held together by various non-covalent forces, including hydrogen bonds and hydrophobic interactions.
The Molecular Components of Heme
The heme group is a non-protein component, or prosthetic group, embedded within a pocket of the globin protein chain. It provides the physical site for oxygen attachment. Heme consists of a large organic ring structure called a porphyrin, specifically protoporphyrin IX, which coordinates a single metal ion.
The central atom of the heme group is iron, the location where oxygen reversibly binds. For hemoglobin to function correctly, the iron atom must be in the ferrous state, designated as Fe\(^{2+}\). When oxygen binds to this Fe\(^{2+}\) ion, it forms oxyhemoglobin, which gives oxygenated blood its bright red color.
If the iron atom is oxidized to the ferric state (Fe\(^{3+}\)), the molecule converts into methemoglobin. In the ferric state, the iron is unable to bind oxygen, rendering that subunit incapable of gas transport. The iron atom is anchored within the porphyrin ring by four nitrogen atoms and is coordinated to a specific histidine residue from the globin chain, known as the proximal histidine.
How Heme Groups Facilitate Oxygen Transport
The presence of four heme groups is responsible for hemoglobin’s efficiency as an oxygen transporter, a function explained by the concept of cooperativity. This mechanism means that the binding of an oxygen molecule to one heme group affects the binding affinity of the other three heme groups in the same molecule. Cooperativity allows hemoglobin to load oxygen effectively in the lungs and unload it efficiently in the tissues.
When no oxygen is bound, the hemoglobin molecule is in a low-affinity state known as the Tense (T) state. The binding of the first oxygen molecule initiates a structural change in that subunit, pulling the iron atom into the plane of the porphyrin ring. This local change is then transmitted across the subunit interfaces, causing the entire tetramer to shift its conformation into the Relaxed (R) state.
The R state has a significantly higher affinity for oxygen, making it easier for subsequent oxygen molecules to bind rapidly. This allosteric transition ensures that at high oxygen levels in the lungs, hemoglobin quickly becomes fully saturated. Conversely, in oxygen-poor tissues, the release of one oxygen molecule destabilizes the R state, favoring a shift back toward the T state. This T-state transition lowers the affinity of the remaining heme groups, promoting the sequential release of the bound oxygen where it is needed.