Heme metabolismmbbs1styearmetabolims.pptx

Heme metabolism

1. CATABOLIC PATHWAY OF HEME TO BILIRUBIN TRANSPORT OF TO LIVER CONJUGATION IN LIVER EXCRETION OF BILIRUBIN

2. Hb is the main hemoprotein present in RBCs Hb Heme Bilirubin Daily 6g of Hb is broken down per day from which 250mg of Bilirubin is formed 50mg of Bilirubin is produced from Myoglobin (Mb) & other heme containing proteins such as cytochromes , catalases , peroxidases etc. So a total of 300mg of Bilirubin is formed per day

3. CATABOLIC PATHWAY OF HEME TO BILIRUBIN It runs in the reticuloendothelial cells of LIVER,SPLEEN AND BONE MARROW Hemoglobin is broken down to HEME & GLOBIN .Globin is further broken down to it’s constituent amino acid for re-utilization RBCs is broken down and hemoglobin is liberated Heme is primarly degraded by microsomal heme oxygenase system,which requires NADPH and cytochrome C.Cytochrome C is for regeneration of NADPH.

4. This Biliverdin is further converted to Bilirubin by an enzyme Biliverdin reductase. One molecule of NADPH is converted to NADP+ This will form linear tetra pyrrole ring of Biliverdin The iron which is liberated from heme ,is in ferrous form and oxidised to ferric and taken up by the transferrin for its re-utilization. One molecule of O2 is required for this process and CO is liberated. The oxygenase enzyme system specifically catalises the cleavage of alpha methynyl bridge which is linking between pyrrole ring 1 & 2

5. The Bilirubin formed in the reticulo -endothelial cells is water insoluble.The lipophilic Bilirubin is therefore transported to plasma bound to Albumin to the liver. 1 molecule of Albumin can bind to 2 molecule of Bilirubin.100ml of plasma can transport upto 25mg of Bilirubin. As the Bilirubin can easily dissociate from Albumin ,the binding of Bilirubin on Albumin can be occupied by drugs like ASPIRIN , PENICILIN etc . Such drugs can therefore easily displace Bilirubin from Albumin .Hence care should be taken while administrating such drugs to avoid KERNIKTERUS . KERNIKTERUS is a rare kind of preventable brain damage that can happen in newborn with Jaundice.

6. Drugs like Primaquine , Novobiocin , Chloramphenicol , Androgens and Pregnanediol may interfere in this conjugation process and cause Jaundice,

7. Excretion of conjugated Bilirubin into bile is mediated By ATP binding cassete protein i.e. MOAT( multispecific organic anion transporter,located in the plasma membrane of biliary canaliculi It is an active process and rate limiting step ,induced by PHENOBARBETONE . FATE OF CONJUGATED BILIRUBIN IN INTESTINE Conjugated bilirubin reaches the intestine through the bile .Intestinal bacteria deconjugate the conjugated bilirubin. This free Bilirubin is further reduced to a colourless tetrapyrrole urobilinogen(UBG) UBG in the large intestine is further reduced to Stercobilinogen(SBG).This SBG is mostly excretd through the feces (250-300mg/day)

8. UBG & SBG are both colourless compound ,but are oxidised to coloured products urobilin and stercobilin respectively by atmospheric oxidation. So the normal colour of faeces & urine is due to these compounds. Since the UBG is passed through blood ,a small amount of UBG ,less than 4mg/day is also excreted in the urine. Around 20% of UBG is reabsorbed from intestine & return to liver by portal blood.These UBG is re-excreted in the bile,it is called ENTEROHEPATIC circulation.

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