Porphyrins, haemoglobin and bilirubin

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Porphyrins, Haemoglobinand Bilirubin
R. C. Gupta M.D. (Biochemistry) Jaip
ur (Rajasthan), India
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E M B - R C G
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E M B - R C G
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Haemoglobin
E M B - R C G
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Myoglobin
E M B - R C G
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Cytochromes
E M B - R C G
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Catalase
E M B - R C G
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Peroxidase
E M B - R C G
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Tryptophan pyrrolase
E M B - R C G
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E M B - R C G
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E M B - R C G
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Synthesis
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E M B - R C G
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E M B - R C G
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E M B - R C G
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Protoporphyrin III is the most abundant porphyrin
It is also the most important porphyrin
E M B - R C G
Haem is synthesized from protopor-phyrin III
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E M B - R C G
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Regulation
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E M B - R C G
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Haemoglobin
E M B - R C G
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E M B - R C G
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E M B - R C G
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E M B - R C G
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E M B - R C G
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E M B - R C G
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E M B - R C G
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E M B - R C G
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E M B - R C G
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E M B - R C G
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Structure of haemoglobin
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Helices in globin chain
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Helix F
Proximal histidine
Haem
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There is a central cavity in the Hb molecule
surrounded by the four polypeptide chains
Central cavity
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2,3-BPG enters the central cavity when its
concentration is high
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b1 - Chain
2,3-BPG
b2 - Chain
2,3-BPG binds to the two b chains by salt bonds
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E M B - R C G
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E M B - R C G
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Co-operative binding
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E M B - R C G
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Myoglobin
Oxygen saturation ()
Haemoglobin
pO2 (mmHg)
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Derivatives of haemoglobin
EMB-RCG
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Oxyhaemoglobin
E M B - R C G
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Carboxyhaemoglobin
E M B - R C G
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E M B - R C G
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Methaemoglobin
E M B - R C G
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E M B - R C G
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E M B - R C G
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E M B - R C G
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Sulphaemoglobin
E M B - R C G
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Abnormal haemoglobins
E M B - R C G
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E M B - R C G
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E M B - R C G
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Haemoglobin S
HbS is formed when the glutamate residue at
position 6 in the b chain is replaced by valine
E M B - R C G
This amino acid residue is present on the surface
of the haemoglobin molecule
Glutamate has a polar side chain while valine has
a non-polar side chain
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E M B - R C G
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Aggregated haemoglobin molecules
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E M B - R C G
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Aggregated haemoglobin molecules distort RBC
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Normal RBC
Sickled RBC
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E M B - R C G
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E M B - R C G
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E M B - R C G
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E M B - R C G
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E M B - R C G
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E M B - R C G
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E M B - R C G
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Haemoglobin MBoston
E M B - R C G
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Thalassaemia
E M B - R C G
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E M B - R C G
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E M B - R C G
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Porphyria
E M B - R C G
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E M B - R C G
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E M B - R C G
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E M B - R C G
Hepatic porphyrias
Erythropoietic porphyrias
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E M B - R C G
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Acute intermittent porphyria
Mode of inheritance Affected enzyme Site of expression
Autosomal dominant Uropor-phyriogen I synthetase Liver cells

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Porphyria cutanea tarda
Mode of inheritance Affected enzyme Site of expression
Autosomal dominant Uropor-phyriogen decarboxylase Liver cells

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Hereditary coproporphyria
Mode of inheritance Affected enzyme Site of expression
Autosomal dominant Copropor-phyriogen oxidase Liver cells

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Variegate coproporphyria
Mode of inheritance Affected enzyme Site of expression
Autosomal dominant Protopor-phyriogen oxidase Liver cells

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Congenital erythropoietic porphyria
Mode of inheritance Affected enzyme Site of expression
Autosomal recessive Uropor-phyriogen III cosynthetase Erythroid cells

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Protoporphyria
Mode of inheritance Affected enzyme Site of expression
Autosomal dominant Ferro-chelatase Liver cells

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E M B - R C G
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Hepatic porphyrias
E M B - R C G
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E M B - R C G
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Erythropoietic porphyrias
E M B - R C G
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E M B - R C G
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Catabolism of haemoglobin
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E M B - R C G
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E M B - R C G
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Jaundice
Serum bilirubin ranges from 0.2-1.0 mg/dl in
concentration
E M B - R C G
This is total bilirubin which includes
Unconjugated bilirubin
Conjugated bilirubin
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E M B - R C G
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Jaundice can occur in a number of diseases
Depending upon the site of the defect, jaundice
can be divided into
E M B - R C G
Post-hepatic jaundice
Hepatic jaundice
Pre-hepatic jaundice
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Pre-hepatic jaundice
E M B - R C G
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E M B - R C G
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E M B - R C G
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Hepatic jaundice
E M B - R C G
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Post-hepatic jaundice
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Due to biliary obstruction, bilirubin conju-gated
in liver
Conjugated bilirubin is regurgitated into
circulation
E M B - R C G
As it is water-soluble, it is excreted in urine
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Gilberts syndrome
E M B - R C G
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Crigler-Najjar syndrome
E M B - R C G
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Lucey-Driscoll syndrome
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Severe unconjugated hyperbilirubinaemia
develops in the newborn
The condition is transient
Phototherapy and, sometimes, exchange transfusion
may be required in the first four days of life
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Rotors syndrome
E M B - R C G
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Dubin-Johnson syndrome
E M B - R C G
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Thank you