Deoxyhemoglobin (dHb) is the form of the oxygen-carrying protein hemoglobin found in red blood cells after it has released its oxygen to the body’s tissues. This molecule is essentially “unloaded” hemoglobin, traveling through the veins back toward the lungs to replenish its supply. Deoxyhemoglobin plays a crucial role in the circulatory system by managing the transport of metabolic byproducts, such as carbon dioxide.
The Molecular Makeup of Deoxyhemoglobin
Hemoglobin is a large protein composed of four subunits, forming a tetramer. Each subunit contains a heme group, a non-protein component that holds a single iron atom in the ferrous state (\(\text{Fe}^{2+}\)). When oxygen is not bound, the protein exists in a low-affinity structural arrangement called the Tense (T) state.
This conformation is characterized by a network of weak bonds, known as salt bridges, that form between the four subunits. These linkages stabilize the molecule, pulling the iron atom out of the plane of the heme ring and decreasing its ability to bind oxygen. This structural shift is the primary difference between deoxyhemoglobin and oxyhemoglobin. When oxygen is available, the salt bridges break, the structure relaxes into the R-state, and the iron atom shifts back into the heme plane, increasing its oxygen binding capability.
The Role in Oxygen Release
Deoxyhemoglobin is formed within the capillaries of metabolically active tissues, such as working muscle, where oxygen demand is high. The physiological conditions in these regions trigger oxygen release. Tissues produce carbon dioxide and metabolic acids, which lower the local blood pH.
This decrease in pH causes specific amino acid residues on the hemoglobin protein to become protonated. This protonation facilitates the formation of the stabilizing salt bridges that characterize the T-state. As the molecule shifts into this Tense state, its affinity for oxygen decreases, forcing the bound oxygen to detach and diffuse into the surrounding tissue.
This mechanism, where increased acidity and carbon dioxide concentration reduce hemoglobin’s oxygen affinity, is known as the Bohr effect. Carbon dioxide also directly stabilizes deoxyhemoglobin by binding to the terminal amino groups of the protein chains, forming carbamate groups. Deoxyhemoglobin plays a role in waste transport, carrying about 10–14% of the carbon dioxide back to the lungs for expiration.
Deoxyhemoglobin as a Clinical Indicator
The concentration of deoxyhemoglobin in the blood serves as a direct indicator of oxygen utilization and is widely used in medical and research settings. This is possible because deoxyhemoglobin and oxyhemoglobin absorb and scatter light differently, giving them distinct color properties. Deoxyhemoglobin absorbs more light in the red and near-infrared spectrum compared to oxyhemoglobin.
Pulse Oximetry
This difference in light absorption is the principle behind the pulse oximeter. By shining two different wavelengths of light through the skin, the device measures the ratio of light absorbed by deoxyhemoglobin versus oxyhemoglobin. The resulting calculation provides a reading of peripheral oxygen saturation, indicating the percentage of hemoglobin carrying oxygen. In situations where deoxyhemoglobin levels are high, a visible sign known as cyanosis may appear, causing the skin and mucous membranes to take on a bluish tint.
Neuroscience Research
The molecule is also utilized in advanced neuroscience research through functional near-infrared spectroscopy (fNIRS). fNIRS measures localized changes in deoxyhemoglobin concentration in the brain to estimate cortical hemodynamic activity. As active brain regions consume oxygen, the resulting increase in deoxyhemoglobin can be tracked in real-time, providing a non-invasive way to study brain function.