HEMOGLOBIN SYNTHESIS, FUNCTION, CATABOLISM AND EXCREATION

We know well that the main function of the red blood cell is to carry oxygen to the tissues and return carbon dioxide to the lungs. This process of gaseous exchange is achieved by the specialized protein in the red blood cell, hemoglobin. Each red blood cell then contains approximately 640 million hemoglobin molecules.

Hemoglobin is an oxygen-binding protein that is mainly found in erythrocytes that aids in transporting oxygen from the lungs to the tissues. The hemoglobins have a molecular weight of about 68,000 and compromises almost one third of the weight of a red blood cell. Each hemoglobin molecule is a tetramer made of four polypeptide globin chains. A heme moiety made up of an organic protoporphyrin ring and a central iron ion in the ferrous state(Fe2+) is found in each globin subunit. Each heme moiety contains an iron molecule that is able to bind and unbind oxygen, enabling the organism to transport oxygen. The most common type of hemoglobin in the adult is HbA, which comprises two alpha-globin and two beta-globin subunits. Different globin genes encode each type of globin subunit.

The two main components for haemoglobin synthesis are globin production and heme synthesis. The synthesis of haem and globin occurs separately. Haem is synthesized largely in the mitochondria, while globin is synthesized in the polyribosomes. Although the synthesis of these two components occur separately within developing red cell precursors, the rates of their synthesis are carefully coordinated for optimal efficiency of the haemoglobin assembly. 

Red Blood Cells; of Haemoglobin, its Creation & Degradation

“Every few seconds, someone, somewhere, needs blood” – By Vanessa Manogaren

 

“A healthy outside starts from the inside.”  – Robert Urich.

Indeed, how wise is the above adage of old.  A healthy person derives from a healthy body, primarily the cells and more significantly the red blood cells. For the body, blood is a necessary element that houses the body’s most vital blood cells. It has a somewhat sticky texture and is literally thicker than water.  This writing aims to emphasize the pivot role red blood cells have in maintaining a safe and healthy blood.

    Red blood cells, also known as erythrocytes, are the blood's cellular building blocks and the oxygen-carrying units that give blood its distinctive colour. A mature human red blood cell has a dumbbell-like form in profile, is tiny, spherical, and biconcave. As it passes through incredibly tiny blood veins, the flexible cell takes on a bell form. Do you know that there are about 640 million haemoglobin molecules in a single red blood cell? A conventional FBC blood laboratory test

can determine the blood's haemoglobin count. Males have a healthy count of 13-18g/Dl, whereas a healthy female has a level of 12-15g/Dl. Hemoglobin, a protein that reversibly binds and moves carbon dioxide and oxygen, is present in the cytoplasm of red blood cells. Hemoglobin is a tetramer that consists of four protein subunits called globin chains. Haem binds to the iron molecule in globin to transport oxygen. Each haemoglobin molecule can carry up to four molecules of oxygen or carbon dioxide since the iron serves the primary role in binding gases.

 

 

A Red Blood Cell's Journey

Synthesis and Function of Erythrocyte

In the bone marrow, the red cell develops in stages. From a hemocytoblast, a multipotent cell in the mesenchyme, it becomes an erythroblast (normoblast). During the course of two to five days of development, the erythroblast progressively occupies with haemoglobin and loses its nucleus and mitochondria, the particles in the cytoplasm that provide the cell's source of energy. Colony Forming Unit – Erythroid (CFU-E), an erythroid stem cell, is produced during the early stages of hematopoiesis The process of erythropoiesis, which is primarily fueled by the hormone erythropoietin, officially starts at this point. For example, when the body tissues lack oxygen, they stimulate the kidney to release the hormone erythropoietin, which in turn increases the production of red blood cells in the bone marrow, and thus increases oxygen delivery to the tissues. CFU-E cells are located in erythroid islands in the bone marrow, where they multiply and develop into mature erythrocytes.

Proerythroblasts, erythroblasts, reticulocytes, and erythrocytes are among the cell generations developed during the differentiation process. The cell, which eventually develops into a completely formed red cell, is known as a reticulocyte in a late stage. Each subsequent cell population is histologically closer to erythrocytes. Eight enzymes work together to synthesize heme in humans. The red blood cell travels through the body in a convoluted manner, passing through the heart twice as it transforms from a deoxygenated blood cell to an oxygenated blood cell. After being synthesized, the red blood cell begins its capillary journey to the heart. Right now, the blood cell is oxygen-depleted. Now that it has reached the heart's vena cava, the deoxygenated red blood cell is forced into the right atrium. The blood cell is subsequently forced past the tricuspid valve and into the right ventricle when the right atrium closes. The red blood cell is then pushed through the semi-lunar by the contraction of the right ventricle. The red blood cell gets to the lungs via the pulmonary artery after exiting the heart. The deoxygenated red blood cell becomes an oxygenated blood cell when it takes up oxygen there. The pulmonary vein leads the blood cell into the left atrium as it travels back to the heart. Red blood cells carry oxygenated blood around the body as they pass through the aorta and enter the kidneys, trunk, and other lower limbs. Before they pass away, they normally live for 120 days. And that's how the whole mechanism works! Despite the fact that it seems to take a while, depending on the person's heart rate, the overall process only takes a minute 
or less.

  

 Haemoglobin: a question of salvaging, metabolism, and redistribution across cell membranes

 

Red blood cells have a finite life span, of approximately 120 days. Erythrocytes' cell membrane deteriorates with time while they are in circulation. Macrophages phagocytose an aged or unviable erythrocyte when they recognize its morphological blueprint. The spleen is the main site of eryptosis, which is the removal of erythrocytes. A physiological number of RBCs are ensured in a healthy body by the balance between eryptosis and erythropoiesis.

      The death of the red blood cell after 120 days marks the beginning of haemoglobin catabolism or breakdown.  As you may know, the two most crucial parts of haemoglobin within an erythrocyte are globin chains and iron-containing heme groups. These elements are separated after being phagocytosed by macrophages. In parallel with the iron being drawn from heme, the polypeptide globin chains are broken down into amino acids, a protein building block that is then used again for protein synthesis. Heme is broken down into biliverdin which is converted into bilirubin, a yellow, insoluble in water, and extremely toxic end product. while iron is then transferred back to the liver and stored there as ferritin by transferrin, a protein mediator. Transferrin plays the role of a mediator akin to trafficking iron across the cell membrane. Hence, the iron molecule is later transported to the bone marrow to be employed in new cycles of erythropoiesis. Bilirubin is eliminated through urine as urobilin and faeces as stercobilin after going through additional changes in the liver and intestines.  For a more comprehensible illustration, watch the video that is featured below.

In essence, the synthesis and catabolism of each haemoglobin in the blood is a complex and extremely detailed-oriented process. I would like to drive home the message that blood formation is an essential and much needed aspect of the human body, as such, we should take every effort to preserve this priceless entity and to champion it for safe blood donation, as the demand for blood is critical and especially needed in surgeries.

Give those who need it this indispensable gift of life!

Video: The Breakdown of Haemoglobin Made Simple

Adapted from, MedsXclusive Learning https://www.youtube.com/watch?v=pd-BTcu00nE 

The Purpose

The need for safe blood is vast, but access to it is scarce. This blog is a Haemopoetic & Lymphoid System coursework of the Bachelors in Medical Science, an initiative of the Faculty of International Medical School, MSU which aims to create awareness and knowledge of the general public on the importance of healthy blood in the human body as well as the anatomy, function and role of red blood cells in haemoglobin synthesis and catabolism. The author aims to inculcate appreciation of people towards every iota of blood in the human body and to champion it for safe blood donation.

 

Reference:

- Chapter 29 production and destruction of erythrocytes. (2011, December 26). Free Medical Textbook. Retrieved Sept 30, 2022 from https://medtextfree.wordpress.com/2011/12/26/chapter-29-production-and-destruction-of-erythrocytes/

- Adamson, J. W. (1996). Regulation of red blood cell production. The American Journal of Medicine, 101(2A), 4S-6S. Retrieved Sept 30, 2022 from https://doi.org/10.1016/s0002-9343(96)00160-x

- Chan, C.-Y., Cheng, C.-F., Shui, H.-A., Ku, H.-C., & Su, W.-L. (2022). Erythrocyte degradation, metabolism, secretion, and communication with immune cells in the blood during sepsis: A review. Tzu Chi Medical Journal, 34(2), 125–133. Retrieved Oct 1, 2022 from https://doi.org/10.4103/tcmj.tcmj_58_21

- Casale, G. P., Khairallah, E. A., & Grasso, J. A. (1980). An analysis of hemoglobin synthesis in erythropoietic cells. Developmental Biology, 80(1), 107–119. Retrieved Oct 1, 2022 https://doi.org/10.1016/0012-1606(80)90502-3

PREPARED BY 

1. NUR ALYSSYA BINTI YUSOFF

2. VANESSA MANOGAREN