Haemoglobin Flashcards
why do we need haemoglobin?
Respiration is the process in which organisms convert nutrients into useful energy in the presence of O2.
In this, O2 must be carried from lungs to tissues
Cells must have an efficient O2 carrying molecule - this is haemoglobin
As well as O2 transport it also transports CO2 and protects against pH change
describe the structure of haemoglobin
A haemoglobin molecule is composed of four protein globin chains, each centred around a haem group.
In most adult haemoglobin, there are two alpha chains and two beta chains.
where does haem, globin, and haemoglobin synthesis mostly take place?
Haem synthesis occurs mainly in mitochondria
Globin synthesis occurs mainly in the polyribosomes
65% haemoglobin is synthesised in the erythroblasts, 35% in the reticulocytes
what is the difference between embryonic and foetal, and adult Hb?
Embryonic and Foetal haemoglobin have a higher affinity for O2
Haem is composed of a _______ ring with Fe2+ in the middle.
Iron is brought to the developing red cells by a carrier protein called _______ which attaches to special binding sites on the surface of these cells.
Transferrin releases ___ and returns back to circulation.
Haem is synthesised from the combining of porphyrin and Fe2+ in the _________
Haem is composed of a PORPHYRIN ring with Fe2+ in the middle.
Iron is brought to the developing red cells by a carrier protein called TRANSFERRIN which attaches to special binding sites on the surface of these cells.
Transferrin releases IRON and returns back to circulation.
Haem is synthesised from the combining of porphyrin and Fe2+ in the MITOCHONDRIA
Lead can bind two key enzymes in the haem synthesis pathway- what are they?
- Porphobilinogen synthase
* Ferrocheletase
As well as causing microcytic anaemia, what is the action of lead on haem sythesis thought to do?
to contribute to the toxic effect on the brain as high ALA is thought to lead to some of the neurological effects of lead poisoning.
what is haem and what does it do in haemoglobin?
The active site is a non-protein group called haem (heme). A haem group sits in the pocket of each hydrophobic globin protein.
It is haem which gives the blood its characteristic red colour. Oxygenated haemoglobin is bright red but deoxygenated haemoglobin is darker red.
Structure of both Haem and Globin are able to be _______.
To hold it in place Fe2+ binds to _ nitrogen atoms in the _______ ring
Fe2+ also needs to bind to O2 and to globin which it does by 2 other binding sites on either side of the ring, one binds to _____ and one binds to a ________ residue on globin Fe2+
Structure of both Haem and Globin are able to be MODIFIED
To hold it in place Fe2+ binds to 4 nitrogen atoms in the PORPHYRIN ring
Fe2+ also needs to bind to O2 and to globin which it does by 2 other binding sites on either side of the ring, one binds to OXYGEN and one binds to a HISTIDINE residue on globin Fe2+
What happens to iron when haemoglobin is oxygenated
Fe2+ moves into the plane of porphyrin ring.
what does oxygenation of 1 haem group do?
changes the shape of the tertiary globin structure
As the four globin molecules of Hb are associated changes to the shape of one globin molecule affects the others in this case so they are more likely to bind O2.
how does Hb’s affinity for oxygen increase?
Oxygen binds to one haemoglobin molecule
This increases the affinity of the 3 remaining molecules to bind O2.
This further increases the the affinity of the remaining 2 molecules to bind O2 which further increases the affinity of the remaining molecule to bind O2
what is cooperativity
Haemoglobin is fully saturated with O2
Oxyhaemoglobin circulates to deoxygenated tissues -what happens?
Here O2 is unloaded and the affinity of Haemoglobin for O2 is decreased
what happens where O2 tensions are very low, e.g. active tissues
the affinity of haemoglobin for O2 is low and maximal delivery of O2 is achieved
what 3 things are needed for regulation of the affinity of haemoglobin for O2?
- CO2
- H+
- 2,3-BPG
When do tissues need more O2 to be delivered to them?
Where tissues have a higher metabolic rate.
How can Hb sense that a tissue need O2
1) If pO2 is low
2) If pCO2 is high
how does CO2 effect oxygenation?
CO2 is in equilibrium with protons in the blood
Therefore an increase in CO2 causes an increase in acidity which decreases O2’s association with Hb
This is the Bhor Effect
An important function of blood is the maintenance of body pH- what is it? What happens if it is outwit the normal range?
Human blood is slightly basic, pH 7.39 – 7.45
In a healthy person, blood pH is never more than 0.2 pH units from its average value
pH < 7.2, “acidosis”; pH > 7.6, “alkalosis”
Death if pH < 6.8 or > 7.8
CO2 can be transported in the blood in three forms- what are they?
- Dissolved in plasma
- Chemically bound to haemoglobin – 20% is carried in RBCs as caraminohaemoglobin (reaction with amino groups of globin)
- Mostly converted into bicarbonate ion and transported in plasma – 70% as bicarbonates
how does CO2 act in erythrocytes
CO2 combines with H2O, then loses a H+ ion to form a bicarbonate ion (HCO3) and transports 70% of carbon dioxide back to the lungs
As glucose is converted to lactate in erythrocytes, what is produced? what does this do?
As glucose is converted to lactate in erythrocytes 2,3BPG is produced
This binds to the tense form of Hb (deoxyHb)
This inhibits Hb HbO2
descrive carbon monoxide binding to Hb?
Binds irreversibly to Hb and so is no longer able to bind to oxygen.
High concentrations use up the bodies supply of Hb
Poisounous as it uses up the body’s supply of Hb.
Combination of CO with Hb bright red carboxyhaemoglobin
Haemoglobin binds CO with an affinity 200xs higher than O2 so small amounts have big effects
0.02% in inspired air leads to headaches and nausea 0.1% leads to unconsciouness Smokers beware – in heavy smokers up to 20% O2 active sites can be bound to CO
what are haemoglobinopathies
Disorders of abnormal hemoglobin synthesis
what 2 things can haemoglobinopathies be caused by
- structural defects (eg, Sickle cell disease) or
* quantitative defects (beta-thalassemia; alphathalassemia)
what is sickle cell anaemia
Inherited chronic haemolytic anaemia
what causes sickle cell anaemia
Mutation of a single amino acid at residue 6 from glutamate to valine in bglobin. This form of Hb in a person with sickle cell is HbS
What is the effect of sickle cell anaemia?
This results in Hb tetramers which tend to aggregate when deoxygenised making the RBC deformed and inflexible. It cannot get around the body so cannot carry O2.
What effect does the HbS have in sickle cell anaemia
- The inflexibility of the sickled erythrocyte stops it flowing freely through the capillaries
- Repeated oxygenation and de-oxygenation leads to irreversible sickling and eventual blocking of the capillaries
what can be the effects of sickle cell anaemia in infancy
o Failure to thrive (due to lack of O2)
o Repeated infections (lack of WBCs)
o Repeated hand- foot syndrome (dactylitis)
o Repeated infection can lead to impaired spleenic function.
what are thalassaemia
Hetergeneous group of genetic disorders resulting from an abnormaility in a or b globin synthesis
Normally Hb is composed of two a and two b globins Abnormalities in the synthesis of 1 of these chains occurs = thalassaemia
