L.4 Structure & Function of Haemoglobin Flashcards
What type of molecule is O2?
Nonpolar molecule
How does Hb affect O2 solubility in blood?
Increases O2 solubility by about 100 fold
What would happen without Hb in terms of blood circulation?
Blood would have to make a complete circuit in less than a second
What percentage of a red cell’s dry weight does Hb constitute?
About 95%
At what stage does Hb synthesis start?
Pro-erythroblast stage
What percentage of Hb synthesis occurs during the nucleated stages of RBC maturation?
65%
What percentage of Hb synthesis occurs during the reticulocyte stage?
35%
Where is haem produced in maturing cells?
In mitochondria and cytosol
Where is globin produced in maturing cells?
In cytosol by ribosomes
What is Hb?
A conjugated globular protein
What are the components of Hb?
Globin and four haem groups
What is the structure of globin in Hb?
A tetramer of two parts of unlike globin polypeptide chains
What is each haem group composed of?
A protoporphyrin ring with an iron atom in the center
How many different types of haemoglobin do adult RBCs have?
Three different types
What is the composition of HbA?
α2β2
What percentage of adult hemoglobin is HbA?
96-98%
What is the composition of HbA2?
α2δ2
What percentage of adult hemoglobin is HbA2?
1.5-3.2%
What is the composition of HbF?
α2γ2
What percentage of adult hemoglobin is HbF?
0.5-0.8%
What is the primary function of myoglobin?
Oxygen-carrying protein of the muscle
Myoglobin is particularly abundant in the muscles of diving mammals, allowing them to use oxygen underwater.
In which animals is myoglobin particularly abundant?
Diving mammals, like seals and whales
Myoglobin allows these animals to continue using oxygen during prolonged underwater periods.
How many polypeptide chains does hemoglobin contain?
Four polypeptide chains
In contrast, myoglobin has only one polypeptide chain.
What additional group do both hemoglobin and myoglobin contain for oxygen binding?
Iron-containing group (haem)
None of the amino acids in these proteins are well suited to bind oxygen alone.
What is the significance of the switch from fetal to adult hemoglobin?
Occurs 3 - 6 months after birth
This transition is crucial for adapting to breathing air after birth.
How many haem groups are present in each hemoglobin molecule?
Four haem groups
Each haem group contains a porphyrin ring with Fe++.
Where is haem synthesized?
In the mitochondria and cytoplasm of the developing normoblast
This synthesis is essential for proper hemoglobin function.
What is the relationship between the rates of globin synthesis and haem synthesis?
1:1 ratio
The rate of globin synthesis matches the rate of haem synthesis.
What is the role of pyridoxal phosphate (vitamin B6) in haem synthesis?
Acts as a coenzyme for the reaction
This reaction is stimulated by EPO.
What is the first step in haem synthesis?
Condensation of glycine and succinyl coenzyme A
This process is catalyzed by the key rate-limiting enzyme δ-aminolaevulinic acid (ALA) synthase.
What ultimately combines with iron to form haem?
Protoporphyrin
Each haem molecule then combines with a globin chain.
What forms a tetramer of hemoglobin?
Four globin chains each with its own haem group
This structure is crucial for the function of hemoglobin.
What is the genetic control of globin synthesis?
Each globin is under separate genetic control
Where is the α gene cluster located?
On the short arm of chromosome 16
How many functional α gene loci are present on each chromosome 16?
2 functional α gene loci
What proportion of the gene product is produced by α1 and α2?
α1 is responsible for 1/3 and α2 for 2/3 of the gene product
What is the length of the α chain produced by the α gene?
141 amino acids
On which chromosome is the β gene locus located?
Chromosome 11
What is the length of the β chain produced by the β gene?
146 amino acids
In normal circumstances, what is the ratio of the product of the α and β, δ, and γ genes?
1:1 ratio
Where are the main sites of protoporphyrin synthesis in the developing red cell?
Mitochondria
From where is iron (Fe) supplied for globin synthesis?
From circulating transferrin
Where are globin chains synthesized?
On ribosomes
How is haem oxygenated in the lungs?
Due to its structure and the difference in partial pressure between the lung and the portal system
How does oxygen cross the thin layer of epithelial cells?
By simple diffusion
What happens to haem as it takes on O2 at the lungs?
It causes a conformational change, allowing the second haem molecule to be oxygenated
What is the term for the phenomenon where subsequent haem molecule oxygenation occurs easier?
Haem-Haem interaction
What is the oxygen saturation of hemoglobin at the lung?
96% saturated
What type of movement does hemoglobin exhibit as it binds and releases O2?
Allosteric movement
What does hemoglobin carry from the lungs to the tissues?
O2
What does venous blood return to the lungs?
CO2
What effect does pH and CO2 concentration have on hemoglobin’s affinity for oxygen?
This is known as the Bohr effect
What occurs to the β-chains of hemoglobin when it is in its deoxygenated state?
They are slightly separated, allowing 2,3-diphosphoglycerate (2,3-DPG) to enter the Hb molecule
What happens to 2,3-DPG when hemoglobin is in its oxygenated state?
It is ejected
What is 2,3-Diphosphoglycerate (2,3-DPG)?
An organic phosphate that controls hemoglobin (Hb) affinity for oxygen
What is the source of 2,3-DPG?
It is derived from anaerobic glycolysis
What is the primary role of 2,3-DPG in the body?
Regulates Hb-O2 release
How does increased 2,3-DPG affect oxygen release?
Increases O2 release
Where is 2,3-DPG located in the hemoglobin molecule?
In the central cavity of Hb
To which part of hemoglobin is 2,3-DPG bound?
Beta chains
What is the function of hemoglobin in relation to oxygen and carbon dioxide?
Delivery and release of oxygen to tissues and facilitation of carbon dioxide excretion
What does the Oxygen Dissociation Curve represent?
Plots Hb saturation against prevailing oxygen tension
What is the P50 value?
The partial pressure of oxygen at 50% saturation
What is the normal P50 value?
26.6 mmHg
What effect does an increase in CO2 have on the oxygen dissociation curve?
Decreases O2 affinity of Hb, shifting the curve to the right
What generates hydrogen (H+) ions in the blood?
CO2 reacting with water
What conditions decrease O2 affinity of hemoglobin?
- Sickle cell anemia
- Increased body temperature
- Increased CO2 levels
What effect does decreased 2,3-DPG levels have on O2 affinity?
Increases O2 affinity, making O2 given up less readily
How does the O2 affinity of HbF compare to HbA?
HbF has a higher affinity for O2 than HbA
Why does HbF have a higher affinity for oxygen?
γ-chains bind to 2,3-DPG more weakly than β-chains
What is the significance of HbF’s high affinity for oxygen?
Facilitates O2 transport from mother to fetus
