Haemoglobin structure and function

Question 1

What is the structure of haemoglobin

Answer 1

4 polypeptide chains; 2 alpha and 2 beta

Question 2

What are haemproteins

Answer 2

A group of specialised proteins that contain haem as a tightly bound prosthetic group

Question 3

What is haem

Answer 3

Is a complex of protoporphyrixin IX and ferrous iron (Fe2+)

Question 4

How is iron held in the centre of haem molecule

Answer 4

By bonds to the 4 nitrogen of a porphyrin ring

Question 5

Where is haemoglobin synthesised

Answer 5

65% in the erythroblasts

35% in the reticulocyte stage

Question 6

How is the synthesis of haemoglobin regulated

Answer 6

Regulated by tissue hypoxia since hypoxia causes the kidneys to increase production of of erythropoietin, which increases RBC and Hb production

Question 7

Where is haem synthesised

Answer 7

In the mitochondria

Question 8

How is iron delivered to the reticulocyte

Answer 8

Transferrin

Question 9

Where are protoporphyrins synthesised

Answer 9

In the mitochondria of RBC precursors

Question 10

What is the synthesis of protoporphyrins regulated by

Answer 10

Mediated by erythropoietin and vitamin B6

Question 11

What makes a haem molecules

Answer 11

Protoporphyrin + Iron

Question 12

Where does globin synthesis occur

Answer 12

The polyribosomes (polysomes)

Question 13

How doe proper globin synthesis depend on genes

Answer 13

The precise order of amino acids in the globin chains is critical to the structure and function of haemoglobin

Question 14

Where are beta-cluster globin genes found

Answer 14

The short arm of chromosome 11

Question 15

Where are alpha-cluster globin genes found

Answer 15

The short arm of chromosome 16

Question 16

What are the different types of beta-cluster genes

Answer 16

Beta, gamma, delta and epsilon genes

Question 17

What are the different types of alpha-cluster genes

Answer 17

Alpha and zeta genes

Question 18

What can mutations to just one amino acid have on a large scale

Answer 18

Sickle cell disease

Question 19

What is the cause of thalassaemias

Answer 19

Reduced synthesis of moral or beta globin chains

Question 20

When does globin synthesis begins

Answer 20

3 weeks after gestation

Question 21

What are the different type of embryonic haemoglobin

Answer 21

Gower I - zeta & epsilon
Gower II - alpha & epsilon
Portland I - zeta & gamma
Portland II - zeta & beta

Question 22

What are the different types of foetal haemoglobin

Answer 22

HbF - alpha & gamma

HbA - alpha & beta

Question 23

What are the different types of adult haemoglobin

Answer 23

HbA2 - alpha & delta
HbF - alpha & gamma
HbA - alpha & beta

Question 24

What happens to the haemoglobin in the embryonic stage and where is it synthesised

Answer 24

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

Question 25

What happens to haemoglobin in the foetal stage and where is it synthesised

Answer 25

Produced by the liver and spleen | Gamma haemoglobin increases but gradually drops before and after birth

Question 26

What happens to haemoglobin in the adult stage and where is it synthesised

Answer 26

Produced by the bone marrow | Beta haemoglobin increases from birth

Question 27

What does haemoglobin act as a buffer

Answer 27

Maintains the blood pH as it changes from oxyhaemoglobin to deoxyhaemoglobin

Question 28

What does globin do

Answer 28

Protects haem from oxidation, gives solubility and permits variation in affinity

Question 29

What happens to haemoglobin when its oxygenated

Answer 29

2,3-DPG is pushed out, the beta chains move closer

Question 30

What happens when oxygen is unloaded

Answer 30

The beta chains are pulled out, permitting the entry of 2,3-DPG resulting in a lower affinity of O2

Question 31

What does the amount O2 bound to haemoglobin and released to tissues depend on

Answer 31

PO2, CO2 and the affinity of haemoglobin for O2

Question 32

What is oxygen affinity

Answer 32

The ease with which haemoglobin binds and releases oxygen

Question 33

What is the shape of the disassociation

Answer 33

Sigmoid shape

Question 34

What is the Bohr effect

Answer 34

In acidic pH, the curve shifts to the right, resulting in an enhanced capacity to release O2 where it is needed

Question 35

What happens in a right shift

Answer 35

- 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

Question 36

What happens in a left shit

Answer 36

- 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

Question 37

What does the normal position of the curve depend on

Answer 37

- 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)

Question 38

What are the 3 mechanisms of carbon dioxide transport

Answer 38

1. Dissolution in the plasma 2. Formation of carbonic acid 3. binding to form carbaminohaemoglobin

Question 39

How does carbon dioxide bind to haemoglobin

Answer 39

Binds irreversibly at the N-terminal group of the alpha chains of Hb Carbonated-Hb has a lower affinity of oxygen affinity