Hemoglobin (Hb) is the iron-containing conjugated protein present inside red blood cells (RBCs). It gives blood its characteristic red color and is responsible mainly for the transport of oxygen from the lungs to tissues and carbon dioxide from tissues back to the lungs. Hemoglobin also contributes significantly to the buffering of blood and therefore helps maintain acid–base balance.
Hemoglobin accounts for a large proportion of the dry weight of the RBC. In healthy adults, blood hemoglobin concentration is generally around 12–17 g/dL, with variation according to age, sex, pregnancy and other physiological factors.
How Hemoglobin Carries Oxygen
Watch how hemoglobin inside red blood cells picks up oxygen in the lungs, carries it through the circulation and releases it to body tissues.
4 globin chains + 4 heme groups
Structure of Hemoglobin
Hemoglobin is made up of two major components: heme and globin. Heme contains an iron atom that is essential for oxygen binding, while globin is the protein component made up of four polypeptide chains.
Each globin chain is associated with one heme group. Therefore, a complete hemoglobin molecule contains four globin chains and four heme groups.
Heme
Heme contains a porphyrin ring surrounding an iron atom. The iron is normally present in the ferrous (Fe2+) state. This form can reversibly bind oxygen. Oxidation of iron to the ferric (Fe3+) state produces methemoglobin, which cannot effectively carry oxygen.
Globin
Globin consists of four polypeptide chains. The major chains involved in normal human hemoglobins are alpha (α), beta (β), gamma (γ) and delta (δ) chains. The particular combination of these chains determines the type of hemoglobin.
Functions of Hemoglobin
1. Transport of Oxygen
Hemoglobin binds oxygen in the lungs to form oxyhemoglobin. This reaction is reversible, allowing hemoglobin to release oxygen in tissues where it is required. The iron remains in the Fe2+ state during normal oxygen binding.
2. Transport of Carbon Dioxide
Hemoglobin contributes to carbon dioxide transport from tissues to the lungs. Some carbon dioxide binds directly to the globin portion of hemoglobin, forming carbaminohemoglobin.
3. Buffer Action
Hemoglobin is an important intracellular buffer in RBCs. It helps bind hydrogen ions generated during carbon dioxide transport and therefore plays an important role in maintaining blood pH.
Normal Types of Hemoglobin
| Type | Globin Chains | Main Feature |
|---|---|---|
| HbA | α2β2 | Major adult hemoglobin |
| HbA2 | α2δ2 | Small fraction of adult hemoglobin |
| HbF | α2γ2 | Predominant fetal hemoglobin |
HbF has a higher affinity for oxygen than HbA. This allows the fetus to obtain oxygen from maternal blood across the placenta. After birth, HbF gradually decreases and HbA becomes the predominant hemoglobin.
Abnormal Hemoglobins
Hemoglobin variants may result from genetic changes affecting globin chains. Important examples include HbS, HbC and HbE. HbS is associated with sickle cell disease, in which abnormal beta chains promote polymerization of deoxygenated hemoglobin and cause sickling of RBCs.
In thalassemia, the problem is primarily reduced synthesis of one or more globin chains. Alpha-thalassemia involves reduced alpha-chain production, whereas beta-thalassemia involves reduced beta-chain production.
Abnormal Hemoglobin Derivatives
Carboxyhemoglobin
Carbon monoxide (CO) binds hemoglobin with a much higher affinity than oxygen and forms carboxyhemoglobin. This reduces oxygen delivery to tissues and can cause severe tissue hypoxia. Important sources include vehicle exhaust, fires, poorly ventilated fuel-burning appliances and tobacco smoke.
Methemoglobin
Methemoglobin forms when the iron in hemoglobin is oxidized from Fe2+ to Fe3+. It cannot normally carry oxygen. Red cells continuously reduce small amounts of methemoglobin back to functional hemoglobin through enzymatic systems, mainly involving NADH-dependent methemoglobin reductase.
Excessive methemoglobin causes methemoglobinemia, which may present with cyanosis and tissue hypoxia. Oxidizing drugs and chemicals, including some local anesthetics and nitrates, can cause it.
Sulfhemoglobin
Sulfhemoglobin forms when sulfur becomes incorporated into hemoglobin. Unlike methemoglobin, sulfhemoglobin cannot readily be converted back to normal hemoglobin. It persists until the affected RBCs are removed from circulation.
Hemoglobin Synthesis
Hemoglobin synthesis begins in erythroid precursor cells in the bone marrow. The heme portion is synthesized through reactions occurring partly in mitochondria and partly in the cytoplasm, while globin chains are synthesized on ribosomes.
Heme synthesis begins with glycine and succinyl-CoA. The first important step is catalyzed by ALA synthase, producing δ-aminolevulinic acid (ALA). A series of enzymatic reactions ultimately produces protoporphyrin IX, which combines with Fe2+ through the enzyme ferrochelatase to form heme.
The four globin chains are synthesized separately and combine with four heme molecules to form the functional hemoglobin molecule.
Destruction of Hemoglobin
RBCs normally survive for approximately 120 days. Old RBCs are removed mainly by macrophages in the spleen, liver and bone marrow. Hemoglobin is separated into globin and heme.
- Globin is broken down into amino acids and reused.
- Iron is recycled and stored mainly as ferritin or hemosiderin or transported for new hemoglobin synthesis.
- Porphyrin is converted through biliverdin to bilirubin, which is transported to the liver for further processing and excretion in bile.
Iron Metabolism
Iron is essential for hemoglobin and myoglobin synthesis and is also required for several enzymes involved in cellular metabolism. Most body iron is present in hemoglobin, with smaller amounts stored in ferritin and hemosiderin or incorporated into myoglobin and other iron-containing proteins.
Dietary Iron
Dietary iron exists mainly as heme iron from animal foods and non-heme iron from plant-based foods and fortified cereals. Heme iron is generally absorbed more efficiently than non-heme iron.
Absorption and Transport
Iron is absorbed mainly in the duodenum and proximal small intestine. Absorbed iron enters the circulation through ferroportin and is transported in plasma bound to transferrin.
Storage and Regulation
Iron is stored mainly as ferritin, with some stored as hemosiderin. The hormone hepcidin, produced by the liver, is a major regulator of systemic iron balance. Increased hepcidin reduces intestinal iron absorption and iron release from storage cells by decreasing ferroportin activity.
- HbA = α2β2
- HbF = α2γ2
- HbF has greater oxygen affinity than HbA.
- Heme contains Fe2+.
- Methemoglobin contains Fe3+.
- Carbon monoxide forms carboxyhemoglobin.
- Ferrochelatase incorporates iron into protoporphyrin IX.
- Transferrin transports iron in plasma.
- Ferritin is the major intracellular storage form of iron.
- Hepcidin is an important regulator of systemic iron availability.
Medical Disclaimer: The information provided in this article is strictly for educational, study, and exam-preparation purposes. It does not constitute professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider for clinical decisions.