Structure and Function of Haemoglobin Flashcards
Why do we need haemoglobin
(2)
O2 is a nonpolar molecule and doesn’t dissolve well in the aqueous environment of the blood
Instead of depending on our lungs and water in our blood to transport oxygen we rely on haemoglobin which enhances O2s solubility in blood x100 times
Hb makes up what percentage of rbcs
Hb constitutes about 95% of rbcs dry weight
When does haemoglobin synthesis begin in rbcs
(3)
Starts at the pro-erythroblast stage
65% of Hb synthesis occurs during nucleated stages of RBC maturation
The remaining 35% occurs during the reticulocyte stage
Where is haem produced in rbcs
Haem is produced in mitochondria and cytosol
Where is globin produced in rbcs
Globin produced in cytosol by ribosomes
What exactly is haemoglobin
A conjugated globular protein consisting of globin and four haem groups
What is globin
A tetramer of two parts of unlike globin polypeptide chains
What is haem
A protoporyphyrin ring with an iron atom in the centre
Describe the structure of haemoglobin
(2)
consists of 4 chains -> 2 alpha chains and 2 non alpha chains
Each of the 4 chains is associated with one haem group located within a hydrophobic crevice
What haemoglobin is found in adults
(3)
Between 96 and 98% of haemoglobin is haemoglobin A
Between 1.5 to 3.2% is haemoglobin A2
Between 0.5 and 0.8% is Haemoglobin F
What is haemoglobin A made of?
2 alpha and 2 beta chains
What is haemoglobin A2 made of?
2 alpha and 2 delta chains
What is haemoglobin F made of?
2 alpha and 2 gamma chains
How many Hb molecules foes an rbc contain
About 280 million
What is the oxygen-carrying protein in muscle
Myoglobin
Write a note on myoglobin
(2)
The carrier of oxygen in the muscle
Abundant in the muscles of diving animals like seals and whales -> allows them to continue to use oxygen when underwater
Compare myoglobin and haemoglobin
(2)
Both have an additional iron-containing (haem) group
Hb contains four polypeptide chains but myoglobin only has one
When is adult haemoglobin produced
Produced after 3-6 months
How many haem groups are in each haemoglobin
4 haem
What does haem contain
Contains a poryphyrin ring which contains F2++
Where is the haem group found
Found within the hydrophobic pocket of the globin chains
What is haem attached to
(4)
Attached to histidine residues of globin
Covalently linked to iron
Attached to an atom within the hydrophobic pocket
Covalently linked to the proximal histidine
Where is haem synthesised
The mitochondria and the cytoplasm of the developing normoblast
Where is globin synthesised
Synthesised by the ribosome
How much of Hb is made up of globin
96%
What happens in B-thalassemia
Don’t produce B-globin chains
Where is the alpha globin gene
Chromosome 16
Where is the beta, gamma, delta globin genes
Chromosome 11
Which globin chain genes are found on chromosome 16
Alpha
Zeta
Which globin chains are found on chromosome 11
Beta
Delta
Gamma
Epsilon
How is haem synthesised
(4)
Glycine and coenzyme A undergo condensation under the action of the key rate limiting enzyme delta-aminolaevulinic acid (ALA) synthase
Pyridoxal phosphate (vitamin B6) is a coenzyme for this reaction which is stimulated by EPO
Protoporyphrin combines with iron in the ferrous (Fe2+) state to form haem, each molecule of which combines with a globin chain made on the polyribosomes
A tetramer of 4 globin chain each with its own haem group in a “pocket” is then formed to make up a haemoglobin molecule
What is the first step in haemoglobin synthesis
Glycine and coenzyme A undergo condensation under the action of the key rate limiting enzyme delta-aminolaevulinic acid (ALA) synthase
What is the limiting enzyme in haemoglobin synthesis
(2)
ALA synthase
Delta-aminolaevulinic acid
What is the second step in the haemoglobin synthesis
Pyridoxal phosphate (vitamin B6) is a coenzyme for this reaction which is stimulated by EPO
What is the chemical name of vitamin B6
Pyridoxal phosphate
What stimulates vitamin B6
EPO
What is the third step in haemoglobin synthesis
(2)
Protoporyphrin combines with iron in the ferrous (Fe2+) state to form haem
Each molecule of which combines with a globin chain made on the polyribosomes
What is the fourth step in haemoglobin synthesis
A tetramer of 4 globin chains each with its own haem group in a “pocket” is then formed to make up a haemoglobin molecule
Describe the genetic control of alpha globin synthesis
(4)
Alpha gene cluster is on the short arm of chromosome 16
There are 2 functional alpha gene loci on each chromosome 16: a1 and 12
a1 is responsible for 1/3 of the gene product
a2 is responsible for 2/3 of the gene product
This produces an a chain which is 141 aa in length
Describe the genetic control of B globin
(2)
B gene locus is on chromosome 11 as well as the 2 gamma and the delta locus
The B gene produces a B chain which is 146 aa in length
What supplies iron for Hb synthesis
Iron is supplied from circulating transferrin
What happens when haem takes on O2
(3)
A conformational change takes place
This allows the second haem molecule to by oxygenated more easily and subsequent haem molecules will by oxygenated easier again
This is known as Haem-Haem interaction
How saturated is haemoglobin in the lung
96% saturated
What is the Bohr effect of Hb
Hb affinity for oxygen is affected by pH and CO2 concentration
What happens to Hb in its deoxygenated state
The two B-chains are slightly separated
2,3-diphosphoglycerate enters the Hb molecule
What is 2,3-DPG
2,3-diphosphoglycerate
What happens to 2,3-diphosphoglycerate when Hb gains oxygen
2,3-diphosphoglycerate is ejected from haemoglobin
Write a note on 2,3-diphosphoglycerate
(3)
Its a product derived from anaerobic glycolysis
A regulator of Hb-O2 release
Increased 2,3-DPG increases O2 release
Where is 2,3-diphosphoglycerate found in haemoglobin
Located in the central cavity of the Hb molecule
Bound to beta chains
What is the function of 2,3-diphosphoglycerate
To delivery and release oxygen to tissues and the facilitation of carbon dioxide excretion
Where in the body is 2,3-diphosphoglycerate low
The lungs
Where in the body is 2,3-diphosphoglycerate high
In tissues
What is the oxygen dissociation curve
A curve that plots the proportion of Hb in its oxygen saturated form on the vertical axis against the prevailing oxygen tension on the horizontal axis
What does the oxygen dissociation curve tell us
Important for understanding how our blood carries and releases oxygen
What does the oxyhaemoglobin dissociation curve tell us
(2)
It relates oxygen saturation (SO2) and partial pressure of oxygen in the blood (PO2)
It determined by Hb affinity for oxygen -> how readily Hb acquires and releases oxygen molecuels into the fluid that surrounds it
What would decrease the O2 affinity of Hb
(3)
An increase in the amount of CO2 in the blood - this results in O2 being given up more easily
Affinity is decreased in sickle cell anaemia
Affinity is decrease by high body temperature
How does high CO2 decrease Hb affinity for O2
(2)
CO2 generates hydrogen ions by reacting with water
Reduced O2 affinity results from the combination of H+ with deoxyhaemoglobin
What increases O2 affinity for Hb
A decrease in 2,3-diphosphoglycerate levels seen in hypoxia -> O2 is given up less readily
Why is the O2 affinity of HbF higher than HbA
This is because y-chains bind to 2,3-diphosphoglycerate more weakly than B-chains
The high affinity of HbF facilitates O2 transport from the mother to the foetus
What are haemoglobinopathies
Inherited conditions
Few arise de-novo -> due to mutation
What may cause haemoglobinopathies
Structural or qualitative defects (SCD/Hb variants)
Quantitative defects (Thalassaemia)
- Hereditary Persistence of Foetal Haemoglobin (HPFH)
What are the two types of haemoglobinopathies
Qualitative and quantitative haemoglobinopathies
What are qualitative haemoglobinopathies
Quality of haemoglobin affected
S-haemoglobin seen in sickle cell anaemia
What are quantitative haemoglobinopathies
Thalassaemia
Quantity of haemoglobin is affected
Not enough B globin chains
