Haemoglobin Structure And Function

Question 1

Haemoglobin

Answer 1

Haemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates.

Question 2

The main functions of the red blood cell:

Answer 2

•Transfer of O2 from lungs to tissue
•Transfer of CO2 from tissue to lungs
Also carries NO bound to thiol group of globin chain

Question 3

How many Hb molecules are in a rbc?

Answer 3

270 million

Question 4

How much Hb does a man have?

Answer 4

13.5g/dl men;

Question 5

How much Hb does a woman have?

Answer 5

12.5g/dl women

Question 6

1g of Hb carries how much O2

Answer 6

1.34ml of O2

Question 7

One Hb molecule carries how many molecules of oxygen?

Answer 7

•4 molecules of oxygen

Question 8

Haemoglobin (Hb) constitutes how much of the red blood cells?

Answer 8

•1/3 of the red blood cells

Question 9

STRUCTURE OF HAEMOGLOBIN

Answer 9

•Adult Hb is made up of a tetramer of four globin chains (α1, β1, α2, β2) each with its own haem group (tetrapyrol ring with an Fe2+ molecule in the middle)

Question 10

Synthesis of Hb:

Where it begins?
Stages?
Parts?
Sites of synthesis?

Answer 10

Synthesis begins in proerythroblast
➢65% at erythroblast stage
➢35% at reticulocyte stage
•Two parts:
➢Haem
➢Globin

•Haem & globin are produced at different sites respectively:
➢Haem in mitochondria
➢Globin in polyribosomes

Question 11

Discuss the process of Haem synthesis

Answer 11

Protoporphyrin ring with an iron atom in centre

*Precursors are succinyl CoA & glycine forming δ-aminolaevulinic acid (ALA)

*Enzyme is ALA synthase (ALA-S), Pyridoxal phosphate acts as a coenzyme
*Aminolaevulinic acid is converted to Porphobilinogen using a synthase (PBGS)
*Porphobilinogen condenses (deaminase, PBGD) to uroporphyrinogen (a tetrapyrrole ring)
Uroporpyhrinogen is converted to coproporphyrinogen by the action of decarboxylase.
Coproporphyrinogen is then converted to protoporphyrin by the action of an oxidase enzyme.
Fe2+ is incorporated into protoporphyrin, catalysed by ferrochelatase

Question 12

Important components of HAEM SYNTHESIS

Answer 12

*Interleukin 3 & erythropoietin induce transcription of ALA-S & PBGD
*ALA-S is a rate limiting enzyme for haem synthesis
*Iron influx & incorporation into haem is well coordinated to ensure no excess of each

Question 13

Genes for globin are essentially arranged in two clusters:

Answer 13

•b- cluster (b, g, d and e globin genes) on the short arm of chromosome 11
•a- cluster (a and z globin genes) on the short arm of chromosome 16

Question 14

When does Globin synthesis start?

Answer 14

Globin synthesis starts at 3rd week of gestation

Question 15

Define each stage of haemoglobin

Answer 15

Embryonic:
Haemoglobin Gower I ( z2e2)
Haemoglobin Portland ( z2g2)
Haemoglobin Gower II (a2e2)
•Fetal : HbF (a2g2), HbA (a2b2)
•Adult : HbA, HbA2 ( a2d2), HbF.

Question 16

REGULATION OF GLOBIN SYNTHESIS

Answer 16

•The locus control region (LCR) or locus activating region (LAR) for β-gene clusters
•HS40 (DNAse 1 hypersensitive site) for α-gene clusters

Question 17

FUNCTIONS OF HAEMOGLOBIN

Answer 17

•Oxygen delivery to the tissues
•Transport of CO2 to lungs
•Buffer of blood PH
•Destruction of Physiologically active NO2

Question 18

Discuss the reaction of Hb and O2

Answer 18

Reaction of Hb & oxygen
•Oxygenation not oxidation
•One Hb can bind to four O2 molecules
•Less than 0.1 sec required for oxygenation
•b chain move closer when oxygenated
•When oxygenated 2,3-DPG is pushed out
•b chains are pulled apart when O2 is unloaded, permitting entry of 2,3-DPG resulting in lower affinity of O2

Question 19

Discuss HB CONFIGURATIONS

Answer 19

•Hb can exist in 2 configurations, deoxy(R) & oxy(T) (T and R stand for tight & relaxed states respectively)

• At some point during the sequential addition of oxygen to the 4 haems, transition from the T to R configuration occurs and the oxygen affinity of the partially liganded molecule increases dramatically.

Question 20

Discuss the HB-OXYGEN DISSOCIATION CURVE

Answer 20

•Sigmoid shape
•Binding of one molecule facilitate the second molecule binding
•P 50 (partial pressure of O2 at which Hb is half saturated with O2) = 26.6mmHg
•It reflects the allosteric properties of haemoglobin (Hb conformation, & it’s O2 affinity changes as each successive molecule of O2 is bound)
•Ensures that oxygen is rapidly taken up at the high oxygen tensions found in the lungs

And is released readily at the low tensions encountered in the tissues.

Question 21

The normal position of curve depends on

Answer 21

Concentration of 2,3-DPG
◦H+ ion concentration (pH)
◦CO2 in red blood cells
◦Structure of Hb

Question 22

Right shift (easy oxygen delivery)

Answer 22

◦High 2,3-DPG
◦High H+ (low pH)
◦High CO2
◦HbS

Question 23

•Left shift (give up oxygen less readily)

Answer 23

◦Low 2,3-DPG
◦HbF

Question 24

CLINICAL CORRELATES

Answer 24

•Anaemia
•Iron deficiency
•Methaemoglobinaemia
•Haemoglobinopathy
•Acid – base balance