Deoxyhemoglobin is the form of hemoglobin that has released its oxygen, playing a direct role in oxygen delivery to tissues. This state is fundamental to ensuring cells receive oxygen for metabolic processes. Understanding deoxyhemoglobin provides insight into the mechanisms governing gas exchange.
The Molecular Architecture of Hemoglobin
Hemoglobin, responsible for oxygen transport in red blood cells, has a complex quaternary structure. It is composed of four subunits: two alpha (α) and two beta (β) chains in adult hemoglobin. Each globin chain cradles a prosthetic heme group.
The heme group is a porphyrin ring with a central iron atom (Fe2+). This iron atom is where oxygen reversibly binds. This arrangement allows hemoglobin to efficiently load oxygen in high concentration areas and release it where levels are lower.
The Cycle of Oxygenation and Deoxygenation
Hemoglobin undergoes structural changes transitioning between deoxygenated and oxygenated states. Deoxyhemoglobin exists in a “Tense” (T) state, exhibiting lower oxygen affinity. The T-state is characterized by a constrained structure, maintained by salt bridges and hydrogen bonds between subunits.
In oxygen-rich areas like the lungs, the first oxygen molecule binds to a heme iron atom. This binding shifts the iron atom into the porphyrin ring’s plane, pulling an associated histidine. This movement initiates a structural rearrangement within the subunit and across the hemoglobin molecule.
Binding of the first oxygen molecule facilitates subsequent oxygen binding, known as cooperative binding. This occurs because initial binding induces a conformational change—a 15-degree rotation of the alpha-beta dimers—transforming the molecule into the “Relaxed” (R) state. The R-state has higher oxygen affinity, making it easier for the remaining three oxygen molecules to bind rapidly.
In oxygen-depleted tissues, the reverse occurs. Lower oxygen concentration prompts oxygen release from oxyhemoglobin, reverting the molecule to its T-state. This transition from the high-affinity R-state back to the low-affinity T-state facilitates oxygen unloading, ensuring tissues receive their metabolic supply.
Regulation of Oxygen Delivery
The body precisely regulates oxygen delivery to tissues with high metabolic activity. The Bohr effect describes how changes in pH and carbon dioxide influence hemoglobin’s oxygen affinity. In active tissues, cellular respiration produces carbon dioxide, which reacts with water to form carbonic acid, decreasing local pH and increasing hydrogen ion concentration.
Increased hydrogen ions bind to specific amino acid residues on hemoglobin, stabilizing the deoxyhemoglobin T-state. This stabilization reduces hemoglobin’s oxygen affinity, prompting oxygen release to tissues. Carbon dioxide can also directly bind to hemoglobin’s N-terminal amino groups, forming carbaminohemoglobin, which further stabilizes the T-state and promotes oxygen unloading.
2,3-bisphosphoglycerate (2,3-BPG), a molecule in red blood cells, also regulates oxygen delivery. 2,3-BPG binds to deoxyhemoglobin’s central cavity, interacting with positively charged amino acids on the beta chains. This binding stabilizes the T-state, lowering hemoglobin’s oxygen affinity and enhancing its release.
Clinical Relevance and Measurement
Understanding deoxyhemoglobin is applicable in clinical settings, particularly for assessing oxygenation status. Pulse oximetry, a non-invasive technique, relies on the distinct light absorption properties of oxyhemoglobin and deoxyhemoglobin. A pulse oximeter emits two wavelengths—red light (660 nm) and infrared light (940 nm)—through a translucent body part like a fingertip.
Deoxygenated hemoglobin absorbs more red light and transmits more infrared light. Conversely, oxygenated hemoglobin absorbs more infrared light and transmits more red light. By measuring the relative absorption of these wavelengths during arterial pulsations, the device calculates the percentage of hemoglobin saturated with oxygen, providing a real-time estimate of blood oxygen levels.
Cyanosis, a bluish discoloration of skin and mucous membranes, is a visible sign of elevated deoxyhemoglobin in capillaries. This discoloration occurs when deoxygenated blood circulates, often indicating tissues are not receiving adequate oxygen. Recognizing cyanosis serves as a clinical indicator of potential hypoxia, prompting further medical evaluation.