1. PORPHYRIN METABOLISM
dr Agus Budiman L.

2. Porphyrins are cyclic compounds formed by the linkage of four pyrrole rings through methenyl bridges.
Characteristic property of porphyrins is the formation of complexes with metal ions e.g. iron porphyrins in heme and magnesium porphrins in chlorophyll.

5. Examples of natural porphyrins in human and animal are hemoglobin, myoglobin, cytochrome c , cytochrome P450, catalase and tryptophan pyrrolase.

6. Heme synthesis begins with production of ALA (δ aminolevulinat) which succinyl-CoA and glycine are the sources and ALA synthase and pyridoxal phosphate( coenzyme) and occurs at mitochondria of living cells. Afterwards with ALA dehydratase (in cytosol) to produce porphobilinogen ( precursor of pyrrole).

9. ALA 1 synthase is the key regulatory enzymes in liver that regulate heme synthesis.
Synthesis of heme from porphobilinogen through ferrochelatase.
Porphyrias are genetic disorders of heme metabolism.

12. -In adult human erythrocyte could live for about 3 months and destroyed mainly in reticuloendothelial cells of liver, spleen and bone marrow.
Catabolism of heme carried out in the microsomal fractions of cells by heme oxygenase complex. Hemin--- heme---biliverdin----bilirubin with NADPH.

13. Bilirubin bound with albumin to go to liver.
Bilirubin uptake in liver with facilitated transport system.
Bilirubin conjugation with glucuronic acid in liver( induced by phenobarbital).
Bilirubin secreted into bile.

15. Three kinds of jaundice (icterus) are
1. hemolytic (prehepatic) icterus.
2. hepatic icterus.
3. obstructive (posthepatic icterus).

16. Unconjugated hyperbilirubinemia:
Neonatal jaundice is a unconjugated hyperbilirubinemia because the enzymes UDP glucuronyl transferase are reduced.
Crigler-Najjar syndrome
Gilbert syndrome
Toxic Hyperbilirubinemia

17. Conjugated hyperbilirubinemia:
Obstructive of the biliary tree.
Dubin-Johnson syndrome.
Rotor syndrome.
In hepatitis : both are unconjugated and conjugated hyperbilirubinemia.