Hemoglobin is a vital protein found in red blood cells (RBCs) that plays a critical role in oxygen transport, carbon dioxide removal, and maintaining acid-base balance in the body. Here’s a detailed look at its synthesis, function, and degradation.
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Hemoglobin Synthesis
Haemoglobin comprises four polypeptide chains, each containing an iron-bound heme group. The synthesis of Hemoglobin involves several steps:
Hemoglobin Structure
- Haemoglobin Molecule:
- Globin Chains: Composed of two alpha (α) and two betas (β) chains (in adult haemoglobin, HbA). In fetal haemoglobin (HbF), the beta chains are replaced by gamma (γ) chains.
- Heme Group: Each globin chain contains one heme group, which consists of an iron (Fe²⁺) atom bound to a porphyrin ring.
Synthesis of Globin Chains
- Gene Expression:
- Alpha Chains: Produced from genes located on chromosome 16.
- Beta Chains: Produced from genes located on chromosome 11.
- Gamma Chains: Produced in fetal life, also on chromosome 11.
- Delta Chains: Present in small amounts in adult haemoglobin A2, also on chromosome 11.
- Transcription and Translation:
- Transcription: Genes encoding the globin chains are transcribed into messenger RNA (mRNA) in the bone marrow’s nucleus of erythroid precursor cells.
- Translation: mRNA is translated into globin proteins in the cytoplasm of erythroid cells.
Synthesis of Heme
- Formation of Porphyrin Ring:
- Synthesis Pathway:
- ALA synthase converts Glycine and succinyl-CoA into aminolevulinic acid (ALA).
- ALA is then converted into porphobilinogen, hydroxymethylbilane, and protoporphyrin IX.
- Iron is incorporated into protoporphyrin IX to form heme by ferrochelatase.
- Synthesis Pathway:
- Heme and Globin Association:
- Heme binds to globin chains in the endoplasmic reticulum and Golgi apparatus of erythroid cells to form functional haemoglobin.
Hemoglobin Assembly
- Tetramer Formation:
- Alpha and Beta Chains: Two α and two β chains (or γ chains in fetal haemoglobin) form the haemoglobin tetramer (HbA or HbF).
- The tetrameric structure of haemoglobin allows for the cooperative binding of oxygen.
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Hemoglobin Function
- Oxygen Transport:
- Binding: Hemoglobin binds oxygen in the lungs with high oxygen partial pressure (pO₂).
- Transport: Oxygenated haemoglobin (oxyhemoglobin) is transported through the bloodstream to tissues and organs.
- Release: In tissues with lower oxygen partial pressure, haemoglobin releases oxygen, which diffuses into cells.
- Carbon Dioxide Transport:
- Binding: Hemoglobin binds carbon dioxide (CO₂) in tissues, forming carbaminohemoglobin.
- Transport: The CO₂ is carried to the lungs, releasing and exhaling.
- Buffering:
- Haemoglobin helps maintain blood pH by buffering hydrogen ions (H⁺) and contributing to the bicarbonate buffer system.
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Hemoglobin Degradation
- Red Blood Cell Lifespan:
- RBCs have an average lifespan of 120 days.
- Old or damaged RBCs are phagocytized by spleen, liver, and bone marrow macrophages.
- Hemoglobin Breakdown:
- Hemoglobin is broken down into biliverdin, bilirubin, and iron.
- Haemoglobin Catabolism:
- Haemoglobin is broken down into heme and globin by macrophages.
- Globin Chains: Broken into amino acids and recycled for protein synthesis.
- Heme: Converted into biliverdin by heme oxygenase and then into bilirubin by biliverdin reductase.
- Bilirubin Processing:
- Unconjugated Bilirubin: Transported to the liver bound to albumin.
- Conjugation: In the liver, UDP-glucuronosyltransferase converts unconjugated bilirubin bilirubin glucuronide into conjugated bilirubin (bilirubin glucuronide).
- Excretion: Conjugated bilirubin is secreted into the bile and excreted into the intestines. Gut bacteria metabolize it into urobilinogen and stercobilin, excreted in urine and faeces.
- Iron Recycling:
- Iron from heme is released as ferric iron (Fe³⁺) and transported by transferrin to the bone marrow for erythropoiesis or stored in the liver and spleen as ferritin.