Haemoglobin Structure and Function Flashcards
Briefly, describe the structure of haemoglobin.
Haemoglobin is a globular haemoprotein, making up about 1/3 of the RBC (haemoproteins are a group of specialised proteins that contain haem as a tightly bound prosthetic group).
It consists of 2 α and 2 β chains, each holding its own haem molecule.
Haem is a complex of protoporphyrin IX and ferrous iron (Fe2+). Iron is held in the centre of the haem molecule by bonds to the four nitrogens of the porphyrin ring.
65% of the haemoglobin in RBCs is synthesised at the erythroblast stage, and 35% at the reticulocyte stage.
How is haemoglobin synthesis regulated?
It is stimulated by tissue hypoxia (when it isn’t getting an adequate supply of oxygen). The hypoxia causes the kidneys to increase the production of Erythropoietin (EPO), which increases RBC and Hb production.
Where does haem synthesis occur?
Haem synthesis occurs largely in the mitochondria.
Describe the chain of events that leads to haem production.
1) IRON DELIVERY AND SUPPLY:
Iron is delivered to the reticulocyte by transferrin.
2) SYNTHESIS OF PROTOPORPHYRINS:
This occurs in the mitochondria of RBC precursors. It is mediated by EPO and Vit B6. This is done to create Protoporphyrin IX.
3) COMBINING TO MAKE HAEM:
Protoporphyrin IX and iron combine to make a haem molecule. Later, the haem can combine with globin to form haemoglobin.
Where does globin synthesis take place?
Globin synthesis occurs in the polyribosomes.
Briefly, describe haemoglobin synthesis.
Simply put, globin mRNA is transcribed from the genes then translated into globin by the polyribosomes.
The proper globin synthesis depends on genes, because the precise order of amino acids in the globin chains is critical to the structure and function of haemoglobin.
Also, the rates of haem and globin synthesis are carefully coordinated to ensure optimal efficiency of haemoglobin assmebly.
Various types of globin combine with haem to form different haemoglobin. Expand (include listing the different haemoglobin during different times of human growth).
There are eight functional globin chains, arranged in two clusters:
- B-CLUSTER (β, γ, δ and ε globin genes) on the short arm of chromosome 11
- A-CLUSTER (α and ζ globin genes) on the short arm of chromosome 16
The functional haemoglobin in humans at different times of growth are: EMBRYONIC: - Gower I (ζ2 ε2) - Gower II (ζ2 γ2) - Portland (α2 ε2)
FOETAL:
- HbF (α2 γ2)
- HbA (α2 β2)
ADULT:
- HbA
- HbA2 (α2 δ2)
- HbF
What makes up adult haemoglobin (including their percentages)?
It is made up of HbA, HbA2 and HbF.
About 96-98% of the haemoglobin is HbA, with HbA2 at 1.5-3.2% and HbF at 0.5-0.8%.
What could happen to the synthesis of globin chains if mutations occur?
Mutations or deletions may lead to:
- abnormal synthesis of globin chains (eg. Sickle Cell Disease)
- reduced rate of synthesis of normal α or β-globin chains (eg. Thalassaemias)
List the functions of haemoglobin.
- to carry oxygen from the lungs to the tissues
- to remove CO2
- buffering action (maintains blood pH as it changes from oxyhaemoglobin to deoxyhaemoglobin)
Describe the oxygen delivery to the tissues.
One Hb molecule can bind to four O2 molecules.
When oxygenated, 2.3-DPG is pushed out; the β-chains move closer.
β-chains are pulled apart when O2 is unloaded, permitting entry of 2,3-DPG resulting in lower affinity of O2.
What does O2 binding to haemoglobin depends on?
The amount of O2 bound to haemoglobin and released to tissues depends on:
- PO2
- PCO2
- affinity of haemoglobin for O2
Oxygen affinity is the ease with which haemoglobin binds and releases oxygen.
Describe oxygen affinity.
It determines the proportion of O2 released to the tissues or loaded onto the cell at a given oxygen pressure.
Increases in oxygen affinity mean that haemoglobin has an increased affinity for O2, so it can bind more and stronger.
Decreases in oxygen affinity causes O2 to be released.
What is the oxygen dissociation curve?
The oxyhaemoglobin dissociation curve relates oxygen saturation (SO2) and partial pressure of oxygen in the blood (PO2), and is determined by what is called “haemoglobin affinity for oxygen”; that is, how readily haemoglobin acquires and releases oxygen molecules into the fluid that surrounds it.
The P50 is the oxygen tension at which haemoglobin is 50% saturated.
What is the Bohr effect?
It states that haemoglobin’s oxygen binding affinity is inversely related both to acidity and to the concentration of carbon dioxide.
This means that, in acidic pH, the curve shifts to the right; this results in an enhanced capacity to release O2 where it is needed.
