Haemoglobin
[Ref: WG21:p536-539; KB:p211]
Haemoglobin structure
- Protein with MW of 64450
- 4 subunits
* Each subunit contains a heme conjugated to a polypeptide (globin)
* 2 pairs of globin in each haemoglobin
* Heme = Iron-containing porphyrin derivative
* Iron = ferrous ion (Fe2+)
- Adult haemoglobin (HbA) has
* 2 alpha chains and 2 beta chains
--> alpha2beta2
- About 2.5% of hemoglobin is HbA2
* 2 alpha chains and 2 delta chains
Other species
- HbA1c
* Small amounts of HbA has glucose attached to the terminal valine in each beta chain
* Used in monitoring diabetes mellitus
- Carboxyhaemoglobin (COHb)
* Hb bound with carbon monoxide
- Sickle cell (HbS)
* Polymerise at low O2 tension --> Haemolysis
* Confers resistance to one type of malaria
* 40% of population in some parts of Africa
- Myoglobin
* Found in red muscles
- Neuroglobin
* Found in brain
- Haem also present in cytochrome c
Haemoglobin synthesis
- 0.3g of Hb is destoryed and synthesized each hour
= 1 x 10^10 RBC per hour
- [KB2:p211] Daily breakdown of Hb = 6g
Steps in Hb synthesis
Condensation of glycine and succinyl-CoA
--> Protoporphyrin
* Catalyzed by delta-aminolaevulinic acid (ALA) synthase
* Co-enzyme: pyridoxal phosphate (vitamin B6)
* This first step is also the rate-limiting step
--> Protoporphyrin combines with iron (Fe2+) to form haem (or heme)
* Catalyzed by ferrochelatase
ALA synthase
- Short halflife (1hr)
- Activity and synthesis of the enzyme is reduced by haem
--> Negative feedback mechanism
In foetal life
Foetal haemoglobin (HbF)
Beta globin only appears after 6 months in foetal life
RBC breakdown
[KB2:p211]
- Most breakdown is by macrophages in reticuloendothelial system, especially spleen
* Some occurs in liver and bone marrow
- 10% of daily red cell breakdown occurs within the blood
--> Hb dissociates into alpha-beta dimers
--> Dimers are bound by haptoglobin
- Haemopexin binds to free haem when haptoglobin is saturated
- Binding is important in preventing renal loss of haem and dimers (thus iron loss)
Haemoglobin breakdown
## Haematology_-_Haemoglobin_breakdown_20050402-02.png
- Haemoglobin
--> Globin + Haem
- Globin --> Amino acids
- Haem --> Iron + protoporphyrin
* By haem oxygenase
- Protoporphyrin --> Carbon monoxide + Biliverdin
- Biliverdin
--> Bilirubin (by biliverdin reductase in macrophages)
--> Carried by albumin in blood
--> Taken up by hepatocytes by facilitated diffusion
--> Conjugated with UPD-glucuronic acid (more soluble)
--> Secreted into bile
--> Enters into GIT with bile
--> Conversion to stercobilinogen and then sterobilin
--> Excreted in faeces
- Some stercobilin is reabsorbed and excreted in kidney as urobilinogen
NB:
- Bilirubin is converted to lumirubin by whitelight
--> Shorter halflife
--> Used to treat jaundice in neonates
- Unconjugated bilirubin = indirect
- Conjugated bilirubin = Direct bilirubin
* Reacts directly in van den Burgh reaction