Haemoglobin structure and function Flashcards
What is the structure of haemoglobin
4 polypeptide chains; 2 alpha and 2 beta
What are haemproteins
A group of specialised proteins that contain haem as a tightly bound prosthetic group
What is haem
Is a complex of protoporphyrixin IX and ferrous iron (Fe2+)
How is iron held in the centre of haem molecule
By bonds to the 4 nitrogen of a porphyrin ring
Where is haemoglobin synthesised
65% in the erythroblasts
35% in the reticulocyte stage
How is the synthesis of haemoglobin regulated
Regulated by tissue hypoxia since hypoxia causes the kidneys to increase production of of erythropoietin, which increases RBC and Hb production
Where is haem synthesised
In the mitochondria
How is iron delivered to the reticulocyte
Transferrin
Where are protoporphyrins synthesised
In the mitochondria of RBC precursors
What is the synthesis of protoporphyrins regulated by
Mediated by erythropoietin and vitamin B6
What makes a haem molecules
Protoporphyrin + Iron
Where does globin synthesis occur
The polyribosomes (polysomes)
How doe proper globin synthesis depend on genes
The precise order of amino acids in the globin chains is critical to the structure and function of haemoglobin
Where are beta-cluster globin genes found
The short arm of chromosome 11
Where are alpha-cluster globin genes found
The short arm of chromosome 16
What are the different types of beta-cluster genes
Beta, gamma, delta and epsilon genes
What are the different types of alpha-cluster genes
Alpha and zeta genes
What can mutations to just one amino acid have on a large scale
Sickle cell disease
What is the cause of thalassaemias
Reduced synthesis of moral or beta globin chains
When does globin synthesis begins
3 weeks after gestation
What are the different type of embryonic haemoglobin
Gower I - zeta & epsilon
Gower II - alpha & epsilon
Portland I - zeta & gamma
Portland II - zeta & beta
What are the different types of foetal haemoglobin
HbF - alpha & gamma
HbA - alpha & beta
What are the different types of adult haemoglobin
HbA2 - alpha & delta
HbF - alpha & gamma
HbA - alpha & beta
What happens to the haemoglobin in the embryonic stage and where is it synthesised
Produced by the yolk sac
Alpha haemoglobin increases and maintains a high concentration throughout, epsilon haemoglobin is initially high and then drops completely before foetal stage
What happens to haemoglobin in the foetal stage and where is it synthesised
Produced by the liver and spleen
Gamma haemoglobin increases but gradually drops before and after birth
What happens to haemoglobin in the adult stage and where is it synthesised
Produced by the bone marrow
Beta haemoglobin increases from birth
What does haemoglobin act as a buffer
Maintains the blood pH as it changes from oxyhaemoglobin to deoxyhaemoglobin
What does globin do
Protects haem from oxidation, gives solubility and permits variation in affinity
What happens to haemoglobin when its oxygenated
2,3-DPG is pushed out, the beta chains move closer
What happens when oxygen is unloaded
The beta chains are pulled out, permitting the entry of 2,3-DPG resulting in a lower affinity of O2
What does the amount O2 bound to haemoglobin and released to tissues depend on
PO2, CO2 and the affinity of haemoglobin for O2
What is oxygen affinity
The ease with which haemoglobin binds and releases oxygen
What is the shape of the disassociation
Sigmoid shape
What is the Bohr effect
In acidic pH, the curve shifts to the right, resulting in an enhanced capacity to release O2 where it is needed
What happens in a right shift
- Increased partial pressure of oxygen; low pH, high 2,3-DPG binding and high temperature
- Decreased affinity for O2
- Hb willing to release O2 to tissues
- E.g. anemia and acidosis
- Even though there may be less RBCs, they act more efficiently to deliver O2 to target
What happens in a left shit
- Decreased partial pressure of oxygen; high pH, low 2,3-DPG binding and low temperature
- Increased affinity for oxygen
- Hb is less willing to release O2 to tissues
- Eg. Presence of abnormal Hb’s, alkalosis
What does the normal position of the curve depend on
- concentration of 2,3-DPG
- H+ ion concentration
- CO2 in RBC
- Structure of Hb
- Standard conditions = 37 C, 7.40 pH and Base excess is 0 (the amount of CO2 needed to neutralise the acid)
What are the 3 mechanisms of carbon dioxide transport
- Dissolution in the plasma
- Formation of carbonic acid
- binding to form carbaminohaemoglobin
How does carbon dioxide bind to haemoglobin
Binds irreversibly at the N-terminal group of the alpha chains of Hb
Carbonated-Hb has a lower affinity of oxygen affinity
