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ALA synthase

*Co-factor?
Succinyl CoA, glycine -> ALA + CO2

*PLP
*In mitochondria
ALA dehydratase

*Co-factor?
2 ALA -> Porphobilinogen

*Zn2+
Porphobilinogen deaminase
4 Porphobilinogen -> Hydroxymethylbilane
Uroporphyrinogen co-synthase
Hydroxymethylbilane -> Uroporphyrinogen III
Uroporphyrinogen decarboxylase
Uroporphyrinogen III -> Coporphyrinogen III
Coporphyrinogen oxidase
Coporphyrinogen III -> Protoporphyrinogen IX
Protoporphyrinogen oxidase
Protoporphyrinogen IX -> Protoporphyrin IX
Ferrochelatase
Protoporphyrin IX -> Heme
Lead poisoning targets
ALA dehydratase (ALA -> Porphobilinogen)

Ferrochelatase (Protophyrinogen IX -> Heme)
ALA synthase

*Co-factor?
Succinyl CoA, glycine -> ALA + CO2

*PLP
*In mitochondria
Cutaneous photosensitivity NOT present in deficiency of which enzymes?
ALA synthase (Succinyl CoA, glycine -> ALA)

ALA dehydratase (ALA -> Porphobilinogen)

Porphobilingen deaminase (Porphobilinogen -> Hydroxymethylbilane)
Variegate porphyria
Protoporphyrinogen oxidase (Protoporphyrinogen IX -> Protoporphyrin IX)
Microsomal heme oxygenase
Heme + NADPH + O2 -> Biliverdin + Fe2+ + CO

*In ER of macrophage
Biliverdin reductase
Biliverdin -> Bilirubin

*Can use NADH or NADPH
UDP-glucoronyl transferase
Bilirubin -> Bilirubin glucoronic acid
MOAT
Bilirubin glucoronic acid (liver) -> Bilirubin glucoronic acid (GI)
Intestinal bacterial
Bilirubin -> Urobilinogen
Urobilinogen derivatives
Urobilinogen -> Stercobilin (feces), urobilin (kidney)
Neonatal jaundice
Caused by low levels of UDP-glucoronyl transferase, so bilirubin can't be dumped into GI, goes into circulation
Kernicterus
Excessively high bilirubin levels

*Treated with UV light, excretes bilirubin without conjugation
Inherited unconjugated hyperbilirubinemia: Effect on UDP-glucoronyl transferase
Crigler-Najjer type I: None
Crigler-Najjer type II: Markedly reduced
Gilbert: Low
Dubin-Johnson syndrome
Excess conjugated bilirubin

Defect in MOAT protein
Hemolytic jaundice
Excessive RBC breakdown, too much unconjugated bilirubin
Obstructive jaundice
Too much conjugated bilirubin, no problem in liver, but blockage of cystic ducts
Hepatocellular jaundice
Too much unconjugated bilirubin, due to liver damage, cancer etc.