Haemoglobin structure and function

Question 1

What is the structure of haemoglobin?

Answer 1

• Globular haemoprotein

* Made up of 1/3 of red blood cell

Question 2

What are haemoproteins?

Answer 2

• Group of specialized protein containing haem as a tightly bound prosthetic group
○ Complex of protoporphyrin IX and Fe2+
○ Iron held in centre of haem to the 4 nitrogen of a porphyrin ring

Question 3

Where is haemoglobin synthesized?

Answer 3

• 65% synthesised in erythroblasts

* 35% at the reticulocyte stage

Question 4

How is haemoglobin synthesis regulated?

Answer 4

○ Stimulated by tissue hypoxia
○ Hypoxia causes kidney to increase production of EPO
§ Increases RBC and Hb production

Question 5

Normal concentration of Hb in adult males

Answer 5

• Adult male:

13.5-16.5g/dl

Question 6

Normal concentration of Hb in adult females

Answer 6

• Adult female:

○ 12.5-15g/dl

Question 7

Where does haem synthesis occur?

Answer 7

• Occurs largely in mitochondria

Question 8

What are the chain of events in haem synthesis?

Answer 8

• Chain of events:
○ Iron delivery and supply:
§ Iron delivered to the reticulocyte by transferrin
○ Synthesis of protoporphyrins:
§ Occurs in mitochondria of RBC precursor
§ Mediated by EPO and vitamin B6
○ Protoporphyrin+iorn=haem

Question 9

Where does globin synthesis occur?

Answer 9

• Occurs in polyribosomes

Question 10

what coordinates optimal efficiency of Hb assembly?

Answer 10

• Optimal efficiency of Hb assembly is coordinated by the rates of haem and globin

Question 11

What does proper globin synthesis depend on?

Answer 11

• Proper globin synthesis depends on genes

Question 12

What are globin chains arranged in?

Answer 12

• 8 functional globin chains, arranged in 2 clusters:
○ B cluster-short arm of chromosome 11

A cluster-short arm of chromosome 16

Question 13

When does globin synthesis start?

Answer 13

• Starts from 3rd week of gestation

Question 14

Embryonic Hb and what chains they’re composed of

Answer 14

• Embryonic:
	○ Hb gower I
		§ 2 zeta and 2 epsilon chains
	○ Hb portland
		§ 2 zeta and 2 gamma chains
	○ Hb Gower II
		§ 2 alpha and 2 epsilon chains

Question 15

Fetal Hb and what chains they’re composed of

Answer 15

• Fetal:
	○ HbF
		§ 2 alpha and 2 gamma
	○ HbA
		§ 2 alpha and 2 beta

Question 16

Adult Hb and what chains are they composed of

Answer 16

○ HbA
○ HbA2
§ 2 alpha and 2 delta chains

HbF

Question 17

Comment on the expression of alpha and beta in adult Hb

Answer 17

• Expression of alpha and beta closely balanced in adult Hb

Question 18

What will mutations and deletion lead to in adult Hb?

Answer 18

• Mutations and deletions may lead to:
○ Abnormal synthesis of globin chain as in sickle cell diseases
○ Reduced rate of synthesis of normal alpha or beta globin chains as in thalassaemia’s

Question 19

what is the function of Hb?

Answer 19

• Carry oxygen from lungs to tissue

* Remove CO2

Question 20

Buffering action of Hb

Answer 20

• Buffering action

○ Maintains pH of blood when oxyhaemoglobin changes to deoxyhaemoglobin

Question 21

How many O2 can a Hb bind?

Answer 21

○ One Hb can bind to 4 O2 molecules

Question 22

How many seconds required for oxgenation of Hb?

Answer 22

○ Less than 0.01 sec required for oxygenation

Question 23

What happens once Hb is oxygenated?

Answer 23

When oxygenated, (2,3)-DPG is pushed out; the beta chains move closer

Question 24

What happens to beta chains when Hb deoxygenated?

Answer 24

○ Beta chains are pulled apart when O2 unloaded, permitting entry of (2,3)-DPG resulting in lower affinity of O2

Question 25

What does amount of O2 bound to haemoglobin and released to tissue depend on?

Answer 25

• PO2
• PCO2
• Affinity of haemoglobin to O2

Question 26

What is oxygen affinity?

Answer 26

• Ease with which haemoglobin binds and releases oxygen

Question 27

What is the Bohr effect?

Answer 27

Alteration in blood pH, shifting oxygen dissociation curve

Question 28

What happens to bohr curve in acidic pH?

Answer 28

• In acidic pH, curve shifts right

○ Results in enhanced capacity to release O2 where its needed

Question 29

Hb-oxygen dissociation curve(Right shift)

Answer 29

• Right shift:
	○ Increased p50
	○ Decreased affinity O2
	○ Hb willing to release O2 to tissue
	○ Like anaemia, acidosis:
                  RBC act more efficiently to deliver O2 to target

Question 30

Hb-oxygen dissociation curve(Left shift)

Answer 30

• Left shift:
○ Decreased p50
○ Increased affinity O2
○ Hb less willing to release O2 to tissue
○ Like presence of abnormal Hb’s, alkalosis

Question 31

Normal position of curve in Hb-oxygen dissociation curve depends on:

Answer 31

○ Concentration of 2,3-DPG
○ pH
○ CO2 in RBC
○ Structure of Hb

Question 32

Standard conditions in Hb-oxygen dissociation curve

Answer 32

○ 37 degrees celcius
○ pH is 7.4
○ BE=0

Question 33

How is CO2 transported?

Answer 33

• Dissolution in the plasma
• Formation of carbonic acid

Binding to carbaminohaemoglobin

Question 34

Mutations in globin

Answer 34

• Gives rise to
○ Target cells
○ Sickle cells