Download SYNTHESIS OF HEMOGLOBIN

SYNTHESIS OF
HEMOGLOBIN
HEMOGLOBIN
Conjugated protein: heme + globin
 Starts in proerythroblast stage.
 Appears in intermediate normoblastic stage.
 Continues until stage of reticulocyte.
 Heme portion is synthesized in mitochondria.
 Globin, protein part, is synthesized in ribosomes.

SYNTHESIS OF HEME:
Step1: inside mitochondria.
 Acetic acid  succinyl CoA
 2 succinyl CoA+ 2 glycine ALA synthetase-> δALA
 Step 2: ALA goes to cytoplasm.
 ALA+ ALA ALA hydrase porphobilinogen.
 Porphobilinogen uroporphobilinogen I synthetase--
uroporphobilinogenI.
 Uroporphobilinogen I porphobilinogenIII cosynthase--
uroporphobilinohen III
 uroporphobilinogenIII uroporphobilinogen decarboxylase coproporphyrinogenIII

Step 3: transport back to mitochondria
 Corpoporphyrinogen III corpoporphyrinogen oxidase -
protoporphyrinogenIX
 Protoporphyrinogen IX protoporphyrinogen oxidase-
protoporphyrin IX
 Protoporphyrin IX + iron- heme.

STEPS
Acetic acid  succinyl CoA
 2 succinyl CoA+ 2 glycine  Pyrrole
 4 Pyrrole  Protoporphyrin IX
 Protoporphyrin IX + Ferrous  heme
 Heme + globin  hemoglobin chain

TYPES OF HB
Hb A  2 alpha + 2 beta
 Hb A2  2 alpha + 2 delta
 Hb F  2 alpha + 2 gamma
 Gower I Hb  2 zeta + 2 epsilon
 Gower II Hb  2 alpha + 2 epsilon

FORMATION OF GLOBIN
Ribosomes produce polypeptide chains.
 4 types: alpha, beta, gama and delta.
 Different on basis of amino acid sequence.
 2 pairs of chains form one globin molecule.
 Each chain is made of 141-146 amino acids.
 Hb-A = 2 alpha, 2 Beta
 Hb-F = 2 alpha, 2 gama.

CONFIGURATION
I polypeptide chain= 1 heme molecule
 After completion
 1 hemoglobin molecule has 4 polypeptide chain
and 4 heme molecules.

DESTRUCTION OF HEMOGLOBIN.
RBCs are destroyed after 120 days.
 Sites of destruction:
 Reticuloendothelial system
 Spleen
 Then Hb is released into plasma.
 Hb degradation in reticuloendothelial system.
 Split into heme and globin.

Globin utilized in the resynthesis of Hb.
 Heme degradation= iron+ porphyrin.
 Iron is stored in body as ferritin and hemosiderin.
 They are reutilized for synthesis of new Hb.
 Porphysin is converted into green pigment=
biliverdin.
 In humans: biliverdin is converted into bilirubin.
 Biliverdin+ bilirubin= bile pigments

IRON METABOLISM:
Iron is essential mineral.
 Important component of protein.
 Required for Hb and myoglobin formation.
 Involved in oxygen transport.
 So required in human body for oxygen transport.
 Required for the synthesis of:

Cytochrome.
 Cytochrome oxidase,
 Peroxidase,
 Catalase.

NORMAL VALUES AND DISTRIBUTION OF IRON IN
BODY:
Total iron in body: 4g.
 In Hb: 65% - 68%.
 Myoglobin: 4%.
 Intracellular oxidative heme compound: 1%
 In plasma as transferrin stored: 0.1%
 Stored in reticuloendothelial system and liver
:25%-30%.
 Bound with transerrin in plasma- 0.1%
 Stored in liver (ferritin and hemosiderin)

DIETARY IRON:
Available in heme and non heme forms.
 Heme:

Present in fish, meat and chicken.
 Absorbed easily from intestine.


Non heme:
Vegetables, grains and cereals.
 Not absorbed easily.

ABSORPTION OF IRON:
Mainly from small intestine.
 Bile is essentail for iron absorption.
 Enterocytes -> pinocytosis -> digested by
lysosomes
 From enterocytes to blood by a protein called
ferroportin.
 Present in ferric form.
 Converted to ferrous and absorbed in blood.
 Ferrous iron -> HCL -> soluble.
 Ferrous acted upon by ferric reductase -> ferric
iron.

TRANSPORT OF IRON:
In blood, ferrous combines with beta globulin
called apotransferrin.
 Iron + apotransferrin -> transferrin.
 Iron binds loosely with globin and can be released
easily at any region of body.

STORAGE OF IRON:
Excess Fe combines with apoferritin to form
ferritin which is stored esp. In liver cells and
Reticuloendithelial cells.
 Small amounts in other cells.
 Cytoplasm ->

Large amount: stored as ferritin.
 Small amount: as hemosidrin when apoferritin pool is
saturated.

DAILY LOSS OF IRON:
1g Hb -> 3.34 mg of iron.
 100 ml blood -> 15gm Hb and 50 mg iron.
 Males: 1mg iron excreted through faeces.
 Females: 50 ml blood loss -> 25 mg iron.
 Loss of blood in haemorrhage.
 Loss of blood in donation:


450ml blood -> 225mg of iron.
REGULATION OF TOTAL IRON IN BODY:
Absorption = excretion.
 Increase iron in body = decrease absorption.
 No apotransferrin formation in liver.
 Reduction in release of iron from transferrin.
 Transferrin is saturated.
 Further absorption is prevented.
