1. PORPHYRIAS  A group of rare disorders caused by deficiencies of enzymes of the heme biosynthetic pathway  Affected individuals have an accumulation of heme precursors (porphyrins), which are toxic at high concentrations  Attacks of the disease are triggered by certain drugs, chemicals, and foods, and also by exposure to sun  Treatment involves administration of hemin, which provides negative feedback for the heme biosynthetic pathway, and therefore, prevents accumulation of heme precursors

2. PORPHYRIAS GLYCINE + SuccinylCoA  -aminolevulinic acid(ALA) Porphobilinogen(PBG) hydroxymethylbilane uroporphyrinogen III coprophyrinogene III Protoporphyrinogene IX protoporphyrin IX Heme ALA synthase ALA dehydratase PBG deaminase Uroporphyrinogen III cosynthase Uroporphyrinogen decarboxylase Coproporphyrinogen oxidase Protoporphyrinogen oxidase Ferrochelatase ALA-dehydratase Deficiency porphyria Acute intermittent porphyria Congenital erythropoietic porphyria Prophyria cutanea tarda Herediatary coproporphyria Variegate porphyria Erythropoietic protoporphyria Mitochondria

3. BLOOD CELLS LIVER Bilirubin diglucuronide (water-soluble) 2 UDP-glucuronic acid via bile duct to intestines Stercobilin excreted in feces Urobilinogen formed by bacteria KIDNEY Urobilin excreted in urine CO Biliverdin IX  Heme oxygenase O2O2 Bilirubin (water-insoluble) NADP + NADPH Biliverdin reductase Heme Globin Hemoglobin reabsorbed into blood Bilirubin (water-insoluble) via blood to the liver INTESTINE Figure 2. Catabolism of hemoglobin

4. Jaundice Normal ranges: (bilirubin) Total bilirubin = 0.2 - 1.2mg/dL Direct bilirubin = less than 0.3mg/dL Indirect bilirubin = less than 0.9mg/dL Two forms Direct bilirubin: Conjugated with glucoronic acid Indirect bilirubin: unconjugated, insoluble in water.

6. A. Hemolytic anemia excess hemolysis  unconjugated bilirubin B. Hepatitis  unconjugated bilirubin  conjugated bilirubin

7. C. Biliary duct stone  conjugated bilirubin (in blood)

8. Lab results of three different causes of Jaundice ConditionSerum BillirubinUrine Urobilinogen Urine Biollirubin Fecal Urobilinogen NormalDirect:0.1-0.4mg/dl Indirect:0.2-0.7mg/dl 0-4mg/24hAbsent40-280mg/24h Hemolytic anemia Indirect (Increase)IncreasedAbsentIncreased HepatitisDirect &Indirect (Increased) Decreased if micro- obstruction present Present if micro- obstruction occurs Decreased Obstructive jaundice Direct(Increased)AbsentPresentTrace to absent

9. Genetic Disorders of Bilirubin Metabolism ConditionDefectBilirubinClinical Findings Crigler-Najjar syndrome-I severely defective UDP-glucuronyltransferase Unconjugated bilirubin  Profound jaundice Dubin- Johnson syndrome abnormal transport of conjugated bilirubin into the biliary system Conjugated bilirubin  Jaundice

10. THANKS