Haemoglobin structure and function Flashcards

(25 cards)

1
Q

what is haemoglobin and what are haemoproteins?

A

→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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what is the structure of haemoglobin?

A

→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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

at what stages is the haemoglobin synthesized?

A

→65% of the haemoglobin in RBCs is synthesised at the erythroblast stage, and 35% at the reticulocyte stage.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

how is haemoglobin synthesis regulated?

A

→ 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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

where does haem synthesis occur?

A

→haem synthesis occurs largely in the mitochondria.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the chain of events that leads to haem production.

A

→ IRON DELIVERY AND SUPPLY:
→Iron is delivered to the reticulocyte by transferrin.

→ 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.

→COMBINING TO MAKE HAEM:
→Protoporphyrin IX and iron combine to make a haem molecule.
→The haem can combine with globin to form haemoglobin.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

where does globin synthesis happen?

A

Globin synthesis occurs in the polyribosomes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

how does haemoglobin synthesis happen?

A

→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.

→the rates of haem and globin synthesis are carefully coordinated to ensure optimal efficiency of haemoglobin assembly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

how are the globin chains arranged? ( describe the clusters)

A

→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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what are the functional haemoglobins at different times of human growth?

A

EMBRYONIC:
→Gower I (ζ2 ε2)
→Gower II (α2 ε2)
→ Portland (ζ2 γ2)

FOETAL:
→ HbF (α2 γ2)
→ HbA (α2 β2)

ADULT:
→HbA
→ HbA2 (α2 δ2)
→ HbF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what makes up adult haemoglobin (including their percentages)?

A

→It is made up of HbA, HbA2 and HbF.
→96-98% of the haemoglobin is HbA,
→HbA2 at 1.5-3.2%
→HbF at 0.5-0.8%.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what could happen to the synthesis of globin chains if mutations occur?

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what are the functions of haemoglobin?

A

→ to carry oxygen from the lungs to the tissues
→ to remove CO2
→buffering action (maintains blood pH as it changes from oxyhaemoglobin to deoxyhaemoglobin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

describe the oxygen delivery to the tissues

A

→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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what does O2 binding to haemoglobin depends on?

A

→ PO2
→PCO2
→ affinity of haemoglobin for O2 Oxygen affinity is the ease with which haemoglobin binds and releases oxygen.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what is oxygen affinity? and what does increased and decreased oxygen affinity mean?

A

→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.

17
Q

what is the oxygen dissociation curve and what is it determined by and what is P50?

A

→The oxyhaemoglobin dissociation curve relates oxygen saturation (SO2) and partial pressure of oxygen in the blood (PO2)

→it is determined by the “haemoglobin affinity for oxygen”

→The P50 is the oxygen tension at which haemoglobin is 50% saturated.

18
Q

what is haemoglobin affinity for oxygen?

A

→ how readily haemoglobin acquires and releases oxygen molecules into the fluid that surrounds it.

19
Q

what is the Bohr effect?

A

→ haemoglobin’s oxygen binding affinity is inversely related both to acidity and to the concentration of carbon dioxide.

→in acidic pH, the curve shifts to the right; this results in an enhanced capacity to release O2 where it is needed.

20
Q

describe what happens during the right shift of an oxygen dissociation curve

A

→increased P50
→ decreased affinity to O2
→ Hb more willing to release O2 to tissue

21
Q

what are examples of situations where the oxygen curve is right shifted?

A

acidosis and anaemia (even though we may have a lowered number of RBCs, they act more efficiently to deliver O2 to the target).

22
Q

describe what happens during the left shift of an oxygen dissociation curve

A

→decreased P50
→ increased affinity to O2 -
→Hb less willing to release O2 to tissue

23
Q

what are examples of situations where the oxygen curve is left shifted?

A

alkalosis and the presence of abnormal haemoglobins.

24
Q

what does the normal position of the curve depend on?

A

→the concentration of 2,3-DPG - H+ ion concentration (pH)
→ CO2 in RBCs
→ the structure of haemoglobin
→The standard conditions are: - TEMP: 37ºC - pH: 7.4 - BASE EXCESS (BE): 0

25
what are the three mechanisms for carbon dioxide transport?
→dissolution in plasma → formation of carbonic acid → binding to carbaminohaemoglobin