Haemoglobin structure and function Flashcards
What is the structure of haemoglobin?
- Globular haemoprotein
* Made up of 1/3 of red blood cell
What are haemoproteins?
• 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
Where is haemoglobin synthesized?
- 65% synthesised in erythroblasts
* 35% at the reticulocyte stage
How is haemoglobin synthesis regulated?
○ Stimulated by tissue hypoxia
○ Hypoxia causes kidney to increase production of EPO
§ Increases RBC and Hb production
Normal concentration of Hb in adult males
• Adult male:
13.5-16.5g/dl
Normal concentration of Hb in adult females
• Adult female:
○ 12.5-15g/dl
Where does haem synthesis occur?
• Occurs largely in mitochondria
What are the chain of events in haem synthesis?
• 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
Where does globin synthesis occur?
• Occurs in polyribosomes
what coordinates optimal efficiency of Hb assembly?
• Optimal efficiency of Hb assembly is coordinated by the rates of haem and globin
What does proper globin synthesis depend on?
• Proper globin synthesis depends on genes
What are globin chains arranged in?
• 8 functional globin chains, arranged in 2 clusters:
○ B cluster-short arm of chromosome 11
A cluster-short arm of chromosome 16
When does globin synthesis start?
• Starts from 3rd week of gestation
Embryonic Hb and what chains they’re composed of
• 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
Fetal Hb and what chains they’re composed of
• Fetal: ○ HbF § 2 alpha and 2 gamma ○ HbA § 2 alpha and 2 beta
Adult Hb and what chains are they composed of
○ HbA
○ HbA2
§ 2 alpha and 2 delta chains
HbF
Comment on the expression of alpha and beta in adult Hb
• Expression of alpha and beta closely balanced in adult Hb
What will mutations and deletion lead to in adult Hb?
• 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
what is the function of Hb?
- Carry oxygen from lungs to tissue
* Remove CO2
Buffering action of Hb
• Buffering action
○ Maintains pH of blood when oxyhaemoglobin changes to deoxyhaemoglobin
How many O2 can a Hb bind?
○ One Hb can bind to 4 O2 molecules
How many seconds required for oxgenation of Hb?
○ Less than 0.01 sec required for oxygenation
What happens once Hb is oxygenated?
When oxygenated, (2,3)-DPG is pushed out; the beta chains move closer
What happens to beta chains when Hb deoxygenated?
○ Beta chains are pulled apart when O2 unloaded, permitting entry of (2,3)-DPG resulting in lower affinity of O2
