Title: Porphyrins, haemoglobin and bilirubin
1Porphyrins, Haemoglobinand Bilirubin
R. C. Gupta M.D. (Biochemistry) Jaip
ur (Rajasthan), India
2E M B - R C G
3E M B - R C G
4Haemoglobin
E M B - R C G
5Myoglobin
E M B - R C G
6Cytochromes
E M B - R C G
7Catalase
E M B - R C G
8Peroxidase
E M B - R C G
9Tryptophan pyrrolase
E M B - R C G
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19Synthesis
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31Protoporphyrin III is the most abundant porphyrin
It is also the most important porphyrin
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Haem is synthesized from protopor-phyrin III
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33Regulation
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36Haemoglobin
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50Structure of haemoglobin
51Helices in globin chain
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54Helix F
Proximal histidine
Haem
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60There is a central cavity in the Hb molecule
surrounded by the four polypeptide chains
Central cavity
612,3-BPG enters the central cavity when its
concentration is high
62b1 - Chain
2,3-BPG
b2 - Chain
2,3-BPG binds to the two b chains by salt bonds
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65Co-operative binding
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69Myoglobin
Oxygen saturation ()
Haemoglobin
pO2 (mmHg)
70Derivatives of haemoglobin
EMB-RCG
71Oxyhaemoglobin
E M B - R C G
72Carboxyhaemoglobin
E M B - R C G
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74Methaemoglobin
E M B - R C G
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78Sulphaemoglobin
E M B - R C G
79Abnormal haemoglobins
E M B - R C G
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83Haemoglobin S
HbS is formed when the glutamate residue at
position 6 in the b chain is replaced by valine
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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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85Aggregated haemoglobin molecules
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87Aggregated haemoglobin molecules distort RBC
88Normal RBC
Sickled RBC
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97 Haemoglobin MBoston
E M B - R C G
98Thalassaemia
E M B - R C G
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102Porphyria
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Hepatic porphyrias
Erythropoietic porphyrias
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109Acute intermittent porphyria
Mode of inheritance Affected enzyme Site of expression
Autosomal dominant Uropor-phyriogen I synthetase Liver cells
110Porphyria cutanea tarda
Mode of inheritance Affected enzyme Site of expression
Autosomal dominant Uropor-phyriogen decarboxylase Liver cells
111Hereditary coproporphyria
Mode of inheritance Affected enzyme Site of expression
Autosomal dominant Copropor-phyriogen oxidase Liver cells
112Variegate coproporphyria
Mode of inheritance Affected enzyme Site of expression
Autosomal dominant Protopor-phyriogen oxidase Liver cells
113Congenital erythropoietic porphyria
Mode of inheritance Affected enzyme Site of expression
Autosomal recessive Uropor-phyriogen III cosynthetase Erythroid cells
114Protoporphyria
Mode of inheritance Affected enzyme Site of expression
Autosomal dominant Ferro-chelatase Liver cells
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116Hepatic porphyrias
E M B - R C G
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119Erythropoietic porphyrias
E M B - R C G
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122Catabolism of haemoglobin
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140 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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145Jaundice 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
146Pre-hepatic jaundice
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158Hepatic jaundice
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163 Post-hepatic jaundice
E M B - R C G
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165Due 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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169Gilberts syndrome
E M B - R C G
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172 Crigler-Najjar syndrome
E M B - R C G
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176 Lucey-Driscoll syndrome
177 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
178 Rotors syndrome
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179Dubin-Johnson syndrome
E M B - R C G
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181Thank you