Podcast
Questions and Answers
What is the life span of a red blood cell (RBC)?
What is the life span of a red blood cell (RBC)?
Which of the following factors is NOT required for the process of hemopoiesis?
Which of the following factors is NOT required for the process of hemopoiesis?
What is the main role of the haem group in proteins such as hemoglobin?
What is the main role of the haem group in proteins such as hemoglobin?
Which of the following conditions is considered an inherited hemolytic anemia?
Which of the following conditions is considered an inherited hemolytic anemia?
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What happens to senescent red blood cells (RBCs) within the body?
What happens to senescent red blood cells (RBCs) within the body?
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What role does iron play in the activity of haemoglobin?
What role does iron play in the activity of haemoglobin?
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What percentage of myoglobin's structure is composed of alpha-helices?
What percentage of myoglobin's structure is composed of alpha-helices?
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Which statement accurately describes myoglobin?
Which statement accurately describes myoglobin?
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Where is the haem group located in myoglobin?
Where is the haem group located in myoglobin?
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What happens to the haem iron during oxygenation of myoglobin?
What happens to the haem iron during oxygenation of myoglobin?
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What percentage of whole blood is composed of plasma?
What percentage of whole blood is composed of plasma?
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Which process is specifically involved in the production of red blood cells?
Which process is specifically involved in the production of red blood cells?
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Where does haematopoiesis primarily occur in adults?
Where does haematopoiesis primarily occur in adults?
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What is the role of haemoglobin in the blood?
What is the role of haemoglobin in the blood?
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Which of the following does NOT represent a component of the formed elements in blood?
Which of the following does NOT represent a component of the formed elements in blood?
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What is the typical pH range of blood?
What is the typical pH range of blood?
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Which of the following best describes the function of blood?
Which of the following best describes the function of blood?
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What is the main liquid component of blood called?
What is the main liquid component of blood called?
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How many polypeptide chains does hemoglobin contain?
How many polypeptide chains does hemoglobin contain?
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What type of hemoglobin is produced mainly during fetal development?
What type of hemoglobin is produced mainly during fetal development?
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Which chromosome carries the gene for the alpha-like chains of hemoglobin?
Which chromosome carries the gene for the alpha-like chains of hemoglobin?
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How does myoglobin compare to hemoglobin in terms of oxygen affinity?
How does myoglobin compare to hemoglobin in terms of oxygen affinity?
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What is indicated by the sigmoidal shape of the hemoglobin oxygen dissociation curve?
What is indicated by the sigmoidal shape of the hemoglobin oxygen dissociation curve?
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At what point does hemoglobin dissociate from oxygen more readily than myoglobin?
At what point does hemoglobin dissociate from oxygen more readily than myoglobin?
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Which hemoglobin variant is considered a minor adult form?
Which hemoglobin variant is considered a minor adult form?
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What is the role of the non-covalent interactions between the subunits of hemoglobin?
What is the role of the non-covalent interactions between the subunits of hemoglobin?
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What effect does a low pH or increased pCO2 have on hemoglobin's affinity for oxygen?
What effect does a low pH or increased pCO2 have on hemoglobin's affinity for oxygen?
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What is the primary role of 2,3-BPG in relation to hemoglobin?
What is the primary role of 2,3-BPG in relation to hemoglobin?
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How does the Bohr effect benefit oxygen delivery in the body?
How does the Bohr effect benefit oxygen delivery in the body?
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What happens to the hemoglobin structure when it binds oxygen?
What happens to the hemoglobin structure when it binds oxygen?
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What effect does the presence of 2,3-BPG have on the oxygen dissociation curve?
What effect does the presence of 2,3-BPG have on the oxygen dissociation curve?
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In what situation would you expect elevated levels of 2,3-BPG in erythrocytes?
In what situation would you expect elevated levels of 2,3-BPG in erythrocytes?
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What type of interactions does 2,3-BPG utilize to bind with deoxy-Hb?
What type of interactions does 2,3-BPG utilize to bind with deoxy-Hb?
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What indicates a high oxygen affinity in hemoglobin?
What indicates a high oxygen affinity in hemoglobin?
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Which growth factor is NOT required for the process of hemopoiesis?
Which growth factor is NOT required for the process of hemopoiesis?
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Which of the following statements is true regarding red blood cell (RBC) lifecycle?
Which of the following statements is true regarding red blood cell (RBC) lifecycle?
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What role does myoglobin serve in the body compared to hemoglobin?
What role does myoglobin serve in the body compared to hemoglobin?
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Which component of hemoglobin is responsible for its oxygen binding capability?
Which component of hemoglobin is responsible for its oxygen binding capability?
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What is the fate of globin after the breakdown of senescent red blood cells?
What is the fate of globin after the breakdown of senescent red blood cells?
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What is the primary role of myoglobin in muscle tissue?
What is the primary role of myoglobin in muscle tissue?
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What distinguishes myoglobin from hemoglobin regarding structure?
What distinguishes myoglobin from hemoglobin regarding structure?
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How does the binding of oxygen affect the positioning of the haem iron in myoglobin?
How does the binding of oxygen affect the positioning of the haem iron in myoglobin?
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Which statement accurately describes the haem group in haemoglobin?
Which statement accurately describes the haem group in haemoglobin?
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What effect does a conformational change in myoglobin have upon oxygen binding?
What effect does a conformational change in myoglobin have upon oxygen binding?
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What percentage of whole blood is formed elements?
What percentage of whole blood is formed elements?
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Which substances are carried away from body tissues by blood?
Which substances are carried away from body tissues by blood?
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At what sites does haemopoiesis primarily occur in adults?
At what sites does haemopoiesis primarily occur in adults?
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During which process is oxygen primarily produced?
During which process is oxygen primarily produced?
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What temperature does blood typically maintain in the human body?
What temperature does blood typically maintain in the human body?
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What component of blood does not contain coagulation factors?
What component of blood does not contain coagulation factors?
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Which component makes up the majority of the formed elements in blood?
Which component makes up the majority of the formed elements in blood?
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What does the pH range of blood indicate about its nature?
What does the pH range of blood indicate about its nature?
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What is the advantage of hemoglobin's sigmoidal oxygen dissociation curve compared to myoglobin's hyperbolic curve?
What is the advantage of hemoglobin's sigmoidal oxygen dissociation curve compared to myoglobin's hyperbolic curve?
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Which hemoglobin variant is predominantly expressed during fetal development?
Which hemoglobin variant is predominantly expressed during fetal development?
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What structural feature influences the cooperative binding of oxygen in hemoglobin?
What structural feature influences the cooperative binding of oxygen in hemoglobin?
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Which genes are responsible for the expression of the beta-like chains of hemoglobin?
Which genes are responsible for the expression of the beta-like chains of hemoglobin?
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What is the characteristic shape of myoglobin's oxygen dissociation curve?
What is the characteristic shape of myoglobin's oxygen dissociation curve?
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Which factor affects the affinity of hemoglobin for oxygen when there is an increase in carbon dioxide levels?
Which factor affects the affinity of hemoglobin for oxygen when there is an increase in carbon dioxide levels?
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How does the presence of 2,3-BPG affect the oxygen dissociation curve of hemoglobin?
How does the presence of 2,3-BPG affect the oxygen dissociation curve of hemoglobin?
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What is the key difference in oxygen binding between hemoglobin and myoglobin?
What is the key difference in oxygen binding between hemoglobin and myoglobin?
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What is the effect of the Bohr effect on hemoglobin's affinity for oxygen?
What is the effect of the Bohr effect on hemoglobin's affinity for oxygen?
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How does an increase in 2,3-BPG concentration affect oxygen delivery?
How does an increase in 2,3-BPG concentration affect oxygen delivery?
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What is the primary role of 2,3-BPG in relation to deoxy-Hb?
What is the primary role of 2,3-BPG in relation to deoxy-Hb?
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What change occurs in the hemoglobin structure upon oxygen binding?
What change occurs in the hemoglobin structure upon oxygen binding?
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What occurs during the cooperativity of hemoglobin in relation to oxygen binding?
What occurs during the cooperativity of hemoglobin in relation to oxygen binding?
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What is indicated by an increased P50 value in the context of hemoglobin?
What is indicated by an increased P50 value in the context of hemoglobin?
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Which statement best represents how pH affects hemoglobin's role in oxygen delivery?
Which statement best represents how pH affects hemoglobin's role in oxygen delivery?
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What effect does 2,3-BPG have on the oxygen dissociation curve?
What effect does 2,3-BPG have on the oxygen dissociation curve?
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What is primarily recycled from senescent red blood cells during their breakdown?
What is primarily recycled from senescent red blood cells during their breakdown?
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Which stem cell characteristic facilitates the exit of cells from the bone marrow into circulation?
Which stem cell characteristic facilitates the exit of cells from the bone marrow into circulation?
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What characterizes the life span of an erythrocyte throughout its cycle?
What characterizes the life span of an erythrocyte throughout its cycle?
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Which growth factor is integral for the process of erythropoiesis?
Which growth factor is integral for the process of erythropoiesis?
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What is a defining feature of anaerobic metabolism compared to aerobic metabolism?
What is a defining feature of anaerobic metabolism compared to aerobic metabolism?
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What structural characteristic differentiates myoglobin from hemoglobin?
What structural characteristic differentiates myoglobin from hemoglobin?
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How does the oxygenation of myoglobin affect the positioning of the haem iron?
How does the oxygenation of myoglobin affect the positioning of the haem iron?
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What is the primary function of haem in myoglobin and hemoglobin?
What is the primary function of haem in myoglobin and hemoglobin?
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Which two characteristics are true about the structure of myoglobin?
Which two characteristics are true about the structure of myoglobin?
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What is the functional significance of the histidines E7 and F8 in myoglobin?
What is the functional significance of the histidines E7 and F8 in myoglobin?
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What percentage of whole blood is composed of formed elements?
What percentage of whole blood is composed of formed elements?
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Where does erythropoiesis primarily occur in children?
Where does erythropoiesis primarily occur in children?
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Which statement accurately describes the function of blood concerning metabolic waste?
Which statement accurately describes the function of blood concerning metabolic waste?
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What is the primary temperature at which blood operates in the human body?
What is the primary temperature at which blood operates in the human body?
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Which sites are primarily involved in the haematopoietic function in adults?
Which sites are primarily involved in the haematopoietic function in adults?
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What is the primary role of erythropoiesis?
What is the primary role of erythropoiesis?
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Which component does blood typically NOT carry away from tissues?
Which component does blood typically NOT carry away from tissues?
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What type of blood cells constitutes the majority of formed elements?
What type of blood cells constitutes the majority of formed elements?
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Which of the following hemoglobin types is characterized by the presence of the zeta chain?
Which of the following hemoglobin types is characterized by the presence of the zeta chain?
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What characteristic shape does the oxygen dissociation curve of hemoglobin exhibit?
What characteristic shape does the oxygen dissociation curve of hemoglobin exhibit?
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What structural feature of hemoglobin allows for cooperative binding of oxygen?
What structural feature of hemoglobin allows for cooperative binding of oxygen?
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Which hemoglobin variant has the highest oxygen affinity?
Which hemoglobin variant has the highest oxygen affinity?
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How many oxygen molecules can one molecule of hemoglobin bind at most?
How many oxygen molecules can one molecule of hemoglobin bind at most?
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In terms of gene expression, which chromosome is responsible for the beta-like chains of hemoglobin?
In terms of gene expression, which chromosome is responsible for the beta-like chains of hemoglobin?
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What insight does a hyperbolic oxygen saturation curve provide regarding a protein's oxygen binding properties?
What insight does a hyperbolic oxygen saturation curve provide regarding a protein's oxygen binding properties?
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Which hemoglobin variant is expressed primarily during embryonic development?
Which hemoglobin variant is expressed primarily during embryonic development?
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Which form of hemoglobin has a higher affinity for oxygen?
Which form of hemoglobin has a higher affinity for oxygen?
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What is the effect of increased pCO2 on hemoglobin's oxygen affinity?
What is the effect of increased pCO2 on hemoglobin's oxygen affinity?
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How does the presence of 2,3-BPG influence the oxygen transport function of hemoglobin?
How does the presence of 2,3-BPG influence the oxygen transport function of hemoglobin?
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What physiological advantage does the Bohr effect provide for oxygen delivery?
What physiological advantage does the Bohr effect provide for oxygen delivery?
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What role does the T-form of hemoglobin play in oxygen release?
What role does the T-form of hemoglobin play in oxygen release?
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If the concentration of 2,3-BPG is elevated, what is the expected effect on oxygen delivery?
If the concentration of 2,3-BPG is elevated, what is the expected effect on oxygen delivery?
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What is the effect of a rightward shift in the oxygen dissociation curve?
What is the effect of a rightward shift in the oxygen dissociation curve?
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Which condition favors the loading of oxygen in the lungs?
Which condition favors the loading of oxygen in the lungs?
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Study Notes
Blood Composition
- Blood is a vital fluid that circulates throughout the body, carrying oxygen, nutrients, and hormones to cells while removing waste products.
- It comprises plasma, a complex aqueous solution containing dissolved gases, salts, proteins, carbohydrates, and lipids, and formed elements, primarily red blood cells (RBCs), platelets, and white blood cells (WBCs).
- The volume of blood in a 70kg man is approximately 5.6 litres.
- Whole blood, when allowed to clot, leaves behind a fluid called serum, which lacks coagulation factors.
Haemopoiesis
- Haematopoiesis is the process of producing new blood cells, including RBCs, WBCs, and platelets.
- In adults, haematopoiesis occurs primarily in the marrow of the pelvis, cranium, vertebrae, and sternum.
- Extramedullary haematopoiesis may occur in the liver, thymus, and spleen if necessary.
- Stem cells in the bone marrow differentiate into a variety of blood cell types, with a single stem cell producing over a million mature cells.
Erythropoiesis
- Erythropoiesis is the process of producing RBCs, typically resulting in 16 mature RBCs from a single proerythroblast.
Erythrocytes (RBCs)
- RBCs are anucleate, have a discoid shape, and have a lifespan of about 120 days.
- Anaemia is a condition characterized by a decrease in hemoglobin concentration below the reference range for age and sex.
- The two most common inherited haemolytic anaemias are glucose-6-phosphate dehydrogenase (G6PD) deficiency and sickle cell anaemia.
The Life Cycle of RBCs
- Senescent RBCs are removed by macrophages in the spleen, liver, and bone marrow.
- Haem components are recycled:
- Globin is broken down into amino acids for reuse.
- Iron is reutilised in the production of new haem.
- Porphyrin is excreted in bile.
Oxygen Binding to Proteins
- Haem groups, composed of protoporphyrin IX and ferrous iron (Fe2+), are essential for oxygen binding by haemoglobin and myoglobin.
- Iron is held in position by 4 nitrogen atoms.
- Fe2+ can form two additional bonds, one with an oxygen molecule and one with a histidine residue in the protein.
Myoglobin
- Myoglobin is a globular protein that acts as an oxygen reservoir in heart and skeletal muscle cells.
- It consists of 153 amino acids and has a molecular weight of 17kDa.
- Myoglobin's structure consists of:
- 75% alpha-helices.
- 8 helices, labelled A-H.
- Non-helical regions.
- Hydrophilic exterior.
- Hydrophobic interior, except for histidines E7 and F8.
Haemoglobin
- Haemoglobin (Hb) is a tetrameric protein found in RBCs, responsible for oxygen transport throughout the body.
- Hb consists of four polypeptide chains, each with a haem group, allowing for the binding of four oxygen molecules.
- The subunits are held together by non-covalent interactions.
Haemoglobin Variant Forms
- HbA is the main adult form of haemoglobin, composed of two alpha and two beta chains (a2b2).
- HbA2 is a minor adult form, composed of two alpha and two delta chains (a2d2).
- HbF is the fetal form of haemoglobin, composed of two alpha and two gamma chains (a2g2).
The Oxygen Dissociation Curve
- Myoglobin has a hyperbolic oxygen dissociation curve, indicating that all sites are fully saturated when oxygen pressure is high.
- Haemoglobin's oxygen dissociation curve has a sigmoidal shape, reflecting the co-operative binding of oxygen to the four subunits.
Co-operativity in Haemoglobin
- Co-operativity refers to the phenomenon where the binding of oxygen to one haem group increases the affinity of the remaining haem groups for oxygen.
- The binding of the fourth oxygen molecule to haemoglobin is approximately 300 times stronger than the binding of the first.
Structural Changes Due to Oxygenation
- Deoxy-Hb exists in a tense (T) conformation, having low affinity for oxygen.
- The binding of oxygen to Hb causes a conformational change to a relaxed (R) conformation, increasing its affinity for oxygen.
Allosteric Effects
- Allosteric effects influence Hb's oxygen binding affinity, including:
- Haem-Haem interaction (cooperativity).
- The Bohr Effect.
- 2,3-Bisphosphoglycerate (2,3-BPG).
The Bohr Effect
- The Bohr Effect describes the phenomenon where Hb's oxygen affinity decreases in the presence of low pH or high carbon dioxide concentrations.
- The effect shifts the oxygen dissociation curve to the right, facilitating oxygen release in tissues and oxygen uptake in the lungs.
2,3-BPG
- 2,3-BPG is a molecule present in RBCs that binds to deoxy-Hb, stabilising its T conformation, and reducing its affinity for oxygen.
- Binding of 2,3-BPG to Hb creates salt bridges with positively charged amino acids, which need to be broken during oxygenation.
- The removal of 2,3-BPG from Hb significantly increases its oxygen affinity.
- 2,3-BPG shifts the oxygen dissociation curve to the right, promoting oxygen release in tissues.
2,3-BPG and Anaemia
- High 2,3-BPG levels in anemia increase oxygen delivery to tissues, compensating for reduced hemoglobin levels.
Blood Composition
- Blood - an organ distributed throughout the body, circulating through the heart, arteries, veins, and capillaries
- Approximately 7-8% of body weight
- Average volume in a 70kg man: 5.6L
- Temperature: 38°C
- Slightly alkaline: pH 7.35 - 7.45
- Two main components: Plasma (~55%) and Formed Elements (~45%)
- Plasma: liquid component containing dissolved solutes, such as gases, salts, proteins, carbs, and lipids
- Formed elements: red cells (erythrocytes), platelets, white cells (leukocytes)
- Serum: remaining fluid after clotting
- Serum lacks coagulation factors
Blood Functions
- Carries oxygen, nutrients, hormones, water, and solutes to tissues
- Carries waste matter, carbon dioxide, and heat away from tissues
Haemopoiesis
- Production and development of new blood cells
- Three main processes: Erythropoiesis (red blood cell production), Leucopoiesis (white blood cell production), Thrombopoiesis (platelet production)
- Significantly more red blood cells than white blood cells in circulation
Sites of Haemopoiesis
- In children: long bone marrow (femur, tibia)
- In adults: pelvis, cranium, vertebrae, sternum
- Extramedullary haematopoiesis: liver, thymus, and spleen may resume haematopoietic function
- Maturation, activation, and some proliferation of lymphoid cells occurs in spleen and lymph nodes
Key Features of Haemopoiesis
- Single stem cell produces >10^6 mature cells
- Stem cells grow and divide in bone marrow
- Lose Cell Adhesion Molecules (CAMs) allowing cells to enter circulation
- Requires growth factors: Erythropoietin, colony stimulating factors, interleukins, thrombopoietin
Erythropoiesis
- Typically one proerythroblast gives rise to ~16 mature red blood cells
Erythrocytes (RBCs)
- Anucleate, discoid shape
- ~120-day lifespan
- 1% destroyed per day
Anaemia
- Decreased Hb concentration below the reference range for age and sex:
- Female: 11.5 – 16.0 g/dL
- Male: 13.5 – 17.5 g/dL
Inherited Haemolytic Anaemias
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency
- Sickle cell anaemia
Life Cycle of RBCs
- Lifespan: ~120 days
- Senescent RBCs removed by macrophages
- Haemoglobin components recycled:
- Globin: amino acids are reutilized
- Iron: reutilized
- Haem: excreted in bile
Aerobic Metabolism
- Multi-cellular organisms require oxygen for aerobic metabolism and storage
- Specialized proteins for oxygen transport: Myoglobin and Haemoglobin
Haem Group
- Oxygen binding in proteins depends on the haem group
- Tightly bound to the protein
- Essential for haemoglobin activity
- Iron (Fe2+) held in position by four nitrogens
- Fe2+ can make two more bonds
Structure of Myoglobin
- Oxygen reservoir in heart and skeletal muscle cells
- 153 amino acids, 17kDa compact protein
- Structure: 75% alpha-helix, 8 helices labelled A-H, non-helical regions (AB, BC etc.)
- Exterior: hydrophilic
- Interior: hydrophobic except histidines E7 & F8
Schematic of Oxygen Binding Site
- Haem sits in a crevice near the surface lined with non-polar residues
- E7: distal His
- F8: proximal His
Conformational Change with Oxygen Binding
- Deoxy-Mb: Haem iron lies 0.3 Å out of plane
- Oxy-Mb: Haem iron lies 0.1 Å out of plane
- Oxygenation moves the haem iron, which moves His F8
- Helix F moves, causing other structural changes
Differences in Haemoglobin and Myoglobin
- Myoglobin: storage protein, binds O2 avidly, dissociates slowly, not co-operative, 1 polypeptide
- Haemoglobin: transports O2 to tissues, transports CO2 and protons away from tissues, 4 polypeptide chains, each chain has a haem group
Gene Expression of the Alpha and Beta Chains
- Genes for alpha and beta chains:
- Alpha-like chains: chromosome 16
- Hb Gower 1 (z2e2)
- Hb F (a2g2)
- Hb A2 (a2d2)
- Hb A (a2b2)
- Beta-like chains: chromosome 11
- e
- Gg
- Ag
- d
- b
- Alpha-like chains: chromosome 16
Hb Variant Forms and Gene Expression
- Hb type | Expression | Chains
- HbA | Adult | a2b2
- HbA2 | Minor adult form | a2d2
- HbF | Foetal | a2g2
- Hb Gower 1 | embryonic | z2e2
- Hb Gower 2 | embryonic | a2e2
- Hb Portland | embryonic | z2g2
Oxygen Dissociation Curve
- Myoglobin: hyperbolic shape, reversible binding of a single oxygen, all sites are full at 100% saturation
- Haemoglobin: sigmoid saturation curve, indicative of co-operative binding
- Myoglobin has a higher affinity for O2 than haemoglobin
- PO2 (partial pressure of oxygen) reflects the amount of oxygen dissolved in blood
O2 Binding to Hb - Sigmoidal Saturation Curve
- Indicates co-operative binding, 'cross-talk' between subunits
- Hb dissociates at a higher partial pressure than Mb, allowing O2 delivery from Hb to Mb
Haem Interactions
- Sigmoidal shape of O2 binding curve due to structural changes initiated at one haem and transmitted to other haem groups
- Affinity of the 4th O2 bound is 300 times greater than the 1st O2 bound
Structural Changes due to Oxygenation
- Tense (T) form: Deoxy-Hb, low affinity, ab dimers held together by ionic bonds
- Relaxed (R) form: Oxy-Hb, high affinity, ab dimers held together by hydrophobic interactions
Allosteric Effects
- Haem-Haem interaction: cooperativity
- Bohr Effect
- 2,3 Bisphosphoglycerate
The Bohr Effect
- O2 is released more easily at low pH or increased pCO2
- Decreases oxygen affinity, stabilizes the deoxy (T) form
- Differential pH gradients (lungs have higher pH than peripheral tissues) favour unloading of O2 in tissues and loading of O2 in lung
- Shifts curve right = P50 increased
2,3-BPG
- Present in erythrocytes at ~equimolar concentrations to Hb
- Binds to deoxy-Hb only, decreasing its affinity for O2
- Binding stabilizes the taut (T) conformation
- Forms salt bridges with positively charged residues on the beta subunits in a central cavity, which are broken during oxygenation
- Hb without 2,3-BPG has high oxygen affinity
2,3-BPG - Effects
- Deoxy-Hb + 2,3-BPG : P50 = 26 Torr
- Deoxy-Hb alone: P50 = 1 Torr
- No 2,3-BPG = high O2 affinity
- 2,3-BPG shifts curve right (allowing O2 release in tissues)
- Elevated 2,3-BPG increases O2 delivery in tissues
Summary
- Blood is a crucial organ, carrying oxygen, nutrients, and waste products throughout the body.
- Haemoglobin, the oxygen-carrying protein in red blood cells, features co-operative binding of oxygen, enabling efficient delivery to tissues.
- Allosteric regulation, including the Bohr effect and 2,3-BPG, fine-tunes oxygen delivery by influencing haemoglobin's affinity for oxygen.
- These processes are essential for maintaining the body's oxygen supply and supporting aerobic metabolism.
Blood Composition and Function
- Blood is a vital tissue that circulates throughout the body, composed of plasma and formed elements.
- Plasma comprises 55% of blood volume: an aqueous solution holding gases, salts, proteins, carbohydrates, and lipids.
- Formed elements, making up 45% of blood, include red blood cells (erythrocytes), platelets, and white blood cells (leukocytes).
- When blood clots, the remaining fluid is called serum.
- Blood carries oxygen, nutrients, hormones, and waste products to and from tissues, regulating temperature and fluid balance.
Haemopoiesis: The Production of Blood Cells
- Haemopoiesis is the process by which new blood cells are produced, categorized as erythropoiesis (red blood cell production), leucopoiesis (white blood cell production), and thrombopoiesis (platelet production).
- In adults, haemopoiesis primarily occurs in the bone marrow of the pelvis, cranium, vertebrae, and sternum.
- Extramedullary haematopoiesis, occurring in the liver, thymus, and spleen, can occur in times of need.
- Haemopoiesis requires growth factors such as erythropoietin, colony-stimulating factors, interleukins, and thrombopoietin.
Erythropoiesis: The Creation of Red Blood Cells
- Erythropoiesis, the production of red blood cells, starts with proerythroblasts and results in approximately 16 mature red blood cells per cell.
Erythrocytes (Red Blood Cells)
- Erythrocytes are anucleate, disc-shaped cells crucial for oxygen transport.
- Erythrocytes have a lifespan of about 120 days, with 1% destroyed daily.
- Anaemia is characterized by a decrease in hemoglobin concentration below the reference range for age and sex.
Life Cycle of Red Blood Cells
- Senescent red blood cells are removed by macrophages, recycling their components.
- Globin, a protein component, is broken down into amino acids for reuse.
- Iron is reutilized in the body.
- Haem is excreted in the bile.
Aerobic Metabolism and Oxygen Transport
- Oxygen is vital for aerobic metabolism, the most efficient form of energy production in multicellular organisms.
- Myoglobin and hemoglobin are specialized proteins for oxygen storage and transport.
Haem Group
- Haem, a critical component in oxygen-binding proteins, is not part of the polypeptide chain.
- It is tightly bound to the protein and essential for the functioning of hemoglobin.
- It has an iron atom (Fe2+) held in position by four nitrogen atoms.
- Fe2+ can form two additional bonds, which is crucial for oxygen binding.
Structure of Myoglobin
- Myoglobin is a storage protein for oxygen in heart and skeletal muscle cells.
- It consists of 153 amino acids and has a compact structure with 75% alpha-helices and 8 labelled helices.
- It is hydrophilic on its exterior and hydrophobic on its interior.
- It has two histidine residues (E7 and F8) that are crucial for oxygen binding.
Oxygen Binding Site in Myoglobin
- The haem group sits in a crevice near the surface of myoglobin, lined by non-polar residues.
- The distal histidine residue (E7) and the proximal histidine residue (F8) contribute to oxygen binding.
Conformational Change During Oxygen Binding
- Deoxy-myoglobin has the haem iron 0.3Å out of plane.
- Oxy-myoglobin has the haem iron 0.1Å out of plane.
- Oxygenation moves the iron atom, which in turn pulls the proximal histidine residue, altering the conformation of the protein.
Differences Between Myoglobin and Haemoglobin
- Myoglobin avidly binds oxygen and dissociates slowly, acting as a storage molecule.
- Myoglobin is not cooperative.
- Myoglobin has a single polypeptide chain.
Haemoglobin
- Haemoglobin is a tetrameric protein with four polypeptide chains, each containing a haem group, allowing it to bind four oxygen molecules.
- The subunits are held together by non-covalent interactions.
- Haemoglobin has two main functions: transporting oxygen to tissues and transporting carbon dioxide and protons away from tissues.
Gene Expression of Alpha and Beta Chains
- Alpha and beta chains are encoded on different chromosomes.
- Alpha-like chains are encoded on chromosome 16, while beta-like chains are encoded on chromosome 11.
- Alpha and beta chains are expressed in a developmental manner:
- Hb Gower 1 (embryonic): z2e2
- Hb Gower 2 (embryonic): a2e2
- Hb Portland (embryonic): z2g2
- Hb F (foetal): a2g2
- Hb A2 (adult): a2d2
- Hb A (adult): a2b2
Oxygen Dissociation Curve
- The oxygen dissociation curve for myoglobin is hyperbolic, reflecting reversible binding of a single oxygen molecule.
- The oxygen dissociation curve for hemoglobin is sigmoid, indicating cooperative binding.
- Haemoglobin's sigmoid shape arises from structural changes that occur when oxygen binds to one haem unit, affecting the affinity of other haem units for oxygen.
- Hemoglobin has a lower affinity for oxygen than myoglobin, facilitating oxygen delivery from hemoglobin to myoglobin.
Structural Changes Due to Oxygenation
- Deoxy-hemoglobin (T-form) has a low affinity for oxygen.
- Oxy-hemoglobin (R-form) has a high affinity for oxygen.
- The transition between the T and R forms involves the breaking of ionic bonds between the alpha-beta dimers and the formation of hydrophobic interactions.
Allosteric Effects
- Haem-Haem interaction refers to the cooperative binding of oxygen to hemoglobin subunits.
- The Bohr effect describes the decreased oxygen affinity of hemoglobin at lower pH or higher pCO2 levels.
- 2,3-Bisphosphoglycerate (2,3-BPG) is a molecule present in red blood cells that binds to deoxy-hemoglobin, stabilizing the T-form and decreasing its oxygen affinity.
The Bohr Effect
- The Bohr effect allows hemoglobin to release oxygen more readily in tissues with low pH or higher pCO2 levels.
- This effect is crucial for efficient oxygen delivery to tissues.
2,3-Bisphosphoglycerate (2,3-BPG)
- 2,3-BPG binds to deoxy-hemoglobin, promoting the release of oxygen in tissues with low oxygen levels.
- Increased levels of 2,3-BPG in situations like low oxygen or anemia increase oxygen delivery to tissues.
- In the absence of 2,3-BPG, hemoglobin has a significantly higher oxygen affinity.
- 2,3-BPG shifts the oxygen dissociation curve to the right, facilitating oxygen release.
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Explore the vital functions and composition of blood in this quiz. Learn about the components that make up blood, including plasma and formed elements, and understand the process of haematopoiesis where new blood cells are produced. This quiz covers crucial concepts related to human physiology and blood production.
