Heme synthesis Flashcards
1
Q
Heme synthesis occurs in?
A
- Liver
- erythrocyte producing cells of bone marrow
2
Q
Heme synthesis pathway summary
A
- ALA formation
- Porphobilinogen formation; MITOCHONDRIA
- Uroporphyrinogen III formation
- Heme formation
- Formation of coproporphyrinogen III
- Formation of Protoporphyrin IX; MITOCHONDRIA
- Formation of heme; MITOCHONDRIA
- Mature RBC lack mitochondria and are unable to synthesize heme
3
Q
ALA Synthase rxn
A
- Rate-limiting step in heme synthesis
- starting materials for heme synthesis: Succinyl-CoA & Glycine
- requires Pyridoxal Phosphate (Vit. B6)
- mitochondria
- End-product inhibition
- If heme production increases more than demand, excess heme is converted to hemin (Fe2+ oxidised to Fe3+)
- Hemin represses Hepatic ALA Synthase expression
2 forms of ALA Synthase:
- Hepatic ALAS1
- undergoes feedback inhibition by hemin
- induced by drugs which induce CYP
- Erythroid ALAS2
- present in bone marrow
- does NOT undergo feedback inhibition by hemin
- NOT induced by drugs which induce CYP
- EPO control; needs Iron
4
Q
ALA Dehyrase rxn
A
- Phorphobilinogen produced
- 1st step for 1 pyrrole ring
- colourless but exposure to light is converted to porphobilin which is coloured
- susceptible to heavy metal poisoning
5
Q
HMB Synthase/PBG Deaminase rxn
A
- Converts: Porphobilinogen -> HMB
- 1st appearance of 4 pyrrole rings
- Acute intermittent porphyria
6
Q
Uroporphyrinogen Decarboxylase rxn
A
- Converts Uroporphyrinogen III -> Coproporphyrinogen III
- formation of heme
- coproporphyrinogen moves into mitochondria
7
Q
Ferrochelatase rxn
A
- formation of heme
- incorporation of ferrous (Fe2+) into protoporphyrin IX ring
- Ferrochelatase affected by lead poisoning
8
Q
Uroporphyrinogen III Synthase rxn
A
- converts HMB -> Uroporphyrinogen III (major product)
- ring closure
- colourless
- Uroporphyrinogen I (minor product)
- undergo auto-oxidation to uroporphyrin I & III (coloured)
- Congenital erythropoeitic porphyria
