Lecture 2
Lecture 2
Lecture 2
Heme Synthesis
Globin synthesis
Dyshaemoglobin
2
INTRODUCTION
In 1862, Felix Seyler identified the respiratory protein
haemoglobin
3
INTRODUCTION
Haemoglobin (Hb) is one of the most studied proteins in the
body
4
INTRODUCTION
Free Hb when released into the plasma, is rapidly salvaged to
preserve its iron and amino acid components
6
BIOSYNTHESIS OF
HAEMOGLOBIN
Haemoglobin is synthesized during most of the erythrocytic
maturation process
9
HEME SYNTHESIS
The type III isomer is converted to coproporphyrinogen III
(CPG) by decaboxylation ( All acetyl groups of UPG are
converted to methyl groups)
10
HEME SYNTHESIS
The final steps, carried out in the mitochondria
11
12
HEME STRUCTURE
Heme consists of a ring of carbon, hydrogen, and nitrogen
atoms called protoporphyrin IX
When the ferrous irons are oxidized to the ferric state, they no
longer can bind oxygen. Oxidized haemoglobin is also called
methemoglobin
13
14 Heme structure
INTRODUCTION TO GLOBIN
BIOSYNTHESIS
Six structural genes code for six globin chains.
The alpha (α) and zeta (δ) globin genes are on the short
arm of chromosome 16; the epsilon (ε), gamma (γ), delta
(δ), and beta (β) globin gene cluster is on the short arm of
chromosome 11
15
GLOBIN BIOSYNTHESIS
Transcription of the globin genes to messenger ribonucleic acid
(mRNA) occurs in the nucleus, and translation of mRNA to the
globin polypeptide chain occurs on ribosomes in the cytoplasm
16
GLOBIN BIOSYNTHESIS
After their release from ribosomes, each globin chain
binds to a heme molecule, then forms a heterodimer
17
GLOBIN BIOSYNTHESIS
Two heterodimers then combine to form a tetramer. This
completes the haemoglobin molecule
18
GLOBIN BIOSYNTHESIS
Owing to a mutation in the promoter region of the δ-globin
gene, production of the δ chain polypeptide is very low
19
ONTOGENY
Haemoglobin composition differs with prenatal gestation
time and postnatal age
20
ONTOGENY
These two chains, when paired with the α and γ chains,
form the embryonic haemoglobins
21
22
Haemoglobin: a tetramer of four globin polypeptide chains, with
23 a heme molecule attached to each chain.
DYSHEMOGLOBINS
Dyshaemoglobins (dysfunctional haemoglobins that are
unable to transport oxygen) include methaemoglobin,
sulfhaemoglobin, and carboxyhaemoglobin
25
METHEMOGLOBIN
Levels of methemoglobin greater than 50% can lead to
coma and death
26
METHEMOGLOBIN
As the oxidant overwhelms the haemoglobin reduction
systems, the level of methaemoglobin increases
29
SULFHEMOGLOBIN
Sulfhemoglobin cannot be converted to normal Hb A; it
persists for the life of the cell.
30
31
CARBOXYHEMOGLOBIN
Carboxyhemoglobin (COHb) results from the combination
of carbon monoxide (CO) with heme iron
35