HB Synthesis and Catabolism
HB Synthesis and Catabolism
HB Synthesis and Catabolism
APPIAH
• Office: SAHS - Rm. SF19
• Contact: 0245900367
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Introduction To Haemoglobin
Haemoglobin is a tetramer of globin chains folded
around four heme groups.
It weighs ~ 64500D.
Composition
• 2 alpha
• 2 non- alpha globin chains.
•Heme = 10%
•Globin= 90%
Heme
group
Globin chains
Hemoglobin consists of globin (two alpha and two beta Iron-containing heme pigment.
polypeptide chains) and four heme groups.
Haemoglobin Function
Hb Portland I (ζ 2 γ2)
A1C α2 (β-N-glucose) 3%
F α2 γ2 <1%
Gower-1 ζ2 ε2 0*
Gower-2 α2 ε2 0*
Portland ζ2 γ2 0*
* Indicates early embryonic form not seen in adults
Haemoglobin Synthesis
• Haem synthesis occurs largely in the mitochondria
• Step 1
1. Heme synthesis begins with condensation of glycine &
succinyl-CoA, with decarboxylation, to form -
aminolevulinic acid (ALA). –occurs in mitochondria
• Pyridoxal phosphate (vitamin B6) is a coenzyme for this
reaction.
ALA Synthase is the committed step & is usually rate-limiting
for the overall pathway..
Step 3
The porphyrin ring is formed by condensation of 4 molecules of
porphobilinogen.
Porphobilinogen Deaminase catalyzes successive PBG condensations,
initiated in each case by elimination of the amino group.
Step 4
Uroporphyrinogen III Synthase converts the linear tetrapyrrole
hydroxymethylbilane to the macrocyclic uroporphyrinogen III.
Step 5
Uroporphyrinogen III converted to coproporphyrinonogen III
enzyme: Uroporhpyrinogen III decarboxylase
- transported back into mitochondria
Step 6
- coproporphyrinonogen is converted to protoporphyrinogen IX,
then to protoporphyrin IX
- enzyme: coproporphyrinonogen oxidative decarboxylase
- occurs in mitochondria
Step 7
Heme is formed by incorporation of iron (Fe+2) by enzyme
ferrochelatase
- partly spontaneous
- ferrochelatase enhances rate
- also inhibited by lead
URO
COPRO
PROTO
Haemoglobin Synthesis
Summary
1. Major sites of heme synthesis liver and bone marrow
(erythroblasts).
2. Matured red blood cells have no mitochondria, so can’t
synthesize heme.
3. The substrates mainly include succinyl-CoA, glycine,
Fe2+ .
3. First and last 3 reactions take place in mitochondria,
others in cytoplasm
OXYGEN DISSOCIATION CURVE (OD
CURVE)
RBCs in systemic arterial blood carry O2 from
lungs to the tissues and return in venous blood
with CO2 to the lungs.
Excreted in feces
• Reflects a generalized
liver (hepatocyte)
dysfunction
• In this case,
hyperbilirubinemia is
usually accompanied by
other abnormalities in
biochemical markers of
liver function
Post-hepatic jaundice
• Caused by an obstruction of the
biliary tree
• In a complete obstruction,
urobilin is absent from the
urine