Hemoglobin is an iron-containing protein responsible for most oxygen transport in the blood of humans and many other animals. In humans, it is concentrated inside red blood cells, where it reversibly binds oxygen in the lungs and releases it to tissues. This delivery supports aerobic cellular respiration. Hemoglobin also participates in carbon dioxide transport and the regulation of blood acidity. Its properties depend on interactions between iron-containing heme groups and the surrounding protein subunits. (medlineplus.gov)
Molecular structure
The principal adult human form, hemoglobin A, consists of four globin subunits: two alpha chains and two beta chains, conventionally written α₂β₂. Each subunit contains a heme group, whose central iron binds one oxygen molecule. A fully oxygenated hemoglobin molecule can therefore carry four oxygen molecules. The protein and heme components work together: heme provides the binding site, while globin controls its chemical environment and responsiveness to oxygen. (medlineplus.gov)
Globin chains are folded sequences of amino acids containing alpha helices. A histidine residue coordinates the heme iron. Oxygen binding changes the position of the iron and nearby protein structures, transmitting movement between subunits. Hemoglobin is consequently not simply four independent oxygen-binding units; its organization allows binding at one site to influence the others. (pdb101.rcsb.org)
Cooperative oxygen binding
Hemoglobin exhibits positive cooperativity: binding oxygen to one subunit increases the tendency of other subunits to bind it. This is an example of allostery, in which a protein’s activity changes through interactions between distinct sites. Oxygen acts as a ligand, and its binding shifts hemoglobin toward configurations with greater oxygen affinity. Oxygen release favors the reverse structural changes. (pdb101.rcsb.org)
The relationship between oxygen partial pressure and hemoglobin saturation forms an S-shaped, or sigmoidal, oxygen-dissociation curve. At the relatively high oxygen partial pressure in the lungs, hemoglobin becomes strongly saturated. At lower pressures in tissues, it releases oxygen. The curve’s relatively flat upper portion supports loading over a range of pulmonary conditions, while its steeper middle portion permits substantial unloading as tissue oxygen pressure falls. Saturation describes the proportion of available binding sites occupied, rather than the total quantity of hemoglobin present. (openstax.org)
Regulation and carbon dioxide transport
Oxygen affinity varies with pH, temperature, and the chemical environment. Lower pH favors oxygen release, a relationship called the Bohr effect. Increasing temperature also promotes unloading. These responses help match oxygen delivery to conditions in active tissues, where oxygen consumption, heat production, and carbon dioxide production can increase. (openstax.org)
The red-cell compound 2,3-bisphosphoglycerate, commonly abbreviated 2,3-BPG, reduces adult hemoglobin’s oxygen affinity. Its interaction with hemoglobin helps prevent the protein from retaining oxygen too strongly during tissue delivery. (pdb101.rcsb.org)
Hemoglobin carries some carbon dioxide through binding to the globin component, forming carbaminohemoglobin; carbon dioxide does not occupy the oxygen-binding position on heme iron. Most blood carbon dioxide is transported as bicarbonate instead. Hemoglobin also binds hydrogen ions, contributing to the blood’s buffering capacity. Deoxygenated hemoglobin carries carbon dioxide and hydrogen ions more readily than oxygenated hemoglobin, helping coordinate gas exchange between tissues and lungs. (openstax.org)
Genes and developmental forms
Different globin chains are encoded by different genes. In humans, the closely related HBA1 and HBA2 genes encode alpha-globin and lie on chromosome 16; HBB encodes beta-globin. Changes in globin production or sequence can alter hemoglobin quantity, structure, or function. (medlineplus.gov)
Fetal hemoglobin, HbF, contains two alpha and two gamma chains, α₂γ₂. Its greater oxygen affinity helps transfer oxygen from maternal blood to fetal blood across the placenta. Gamma chains interact less strongly with 2,3-BPG than adult beta chains do. After birth, developmental changes in gene expression progressively replace most HbF with adult hemoglobin. (pdb101.rcsb.org)
Variants and disorders
Inherited sequence changes, or mutations, can produce hemoglobin variants. In sickle cell disease, hemoglobin S contains a beta-chain substitution in which valine replaces glutamate at position six in the traditional mature-chain numbering. Under deoxygenated conditions, hemoglobin S can assemble into fibers that distort red blood cells and contribute to their premature destruction. (pdb101.rcsb.org)
Thalassemias involve reduced production of particular globin chains rather than a single shared structural alteration. Alpha- and beta-chain deficiencies disturb balanced hemoglobin assembly and can cause anemia. Disease severity varies with the affected genes and the extent of reduced globin production. (medlineplus.gov)
Laboratory measurement
A hemoglobin test measures its concentration in blood and is usually included in a complete blood count. Low concentrations can indicate anemia, but concentration alone does not establish its cause. Tests that separate different hemoglobin forms, including electrophoresis, help identify inherited hemoglobin disorders. These measurements address different questions: total concentration concerns the amount present, whereas fractionation concerns the kinds of hemoglobin present. (medlineplus.gov)
Hemoglobin A1c is hemoglobin with attached glucose. Its measurement reflects average blood glucose over approximately three months and is used in the assessment of diabetes mellitus. Some hemoglobin variants and conditions that alter red-cell survival can affect A1c results, so the value is not determined by glucose exposure alone. (niddk.nih.gov)