Heme Synthesis, Porphyria, Lead Poisonong Flashcards
Porphyrias?
Hereditary or acquired conditions of defective heme synthesis that lead to the accumulation of heme precursors (lead poisoning is a similar condition)
Heme synthesis reactions and enzymes (and where)
Glycine + succinyl coa +B6 –> δ-ALA (δ-ALA synthase)
–> porphobilinogen (δ-ALA dehydratase) –> hydroxymethylbilane (porphobilinogen deaminase)
–> uroporphyrinogen III –> coproporphyrinogen III (uroporphyrinogen decarboxylase) –> protoporphyrin + iron –> heme (ferrochelatase)
all in cytoplasm except:
δ-ALA syntase amd ferrochelatase –> mit
Lead poisoning - enzyme affected (and where)
- Ferrochelatase (mit)
2. ALA dehydratase (cytoplasm)
Lead poisoning - accumulation substrates
Protoporphyrin, δ-ALA (blood)
Lead poisoning - way of exposure and neurological symptoms (children and adults)
Children –> exposure to lead paint –> mental deterioration
Adults –> environmental exposure (batteries ammunition) –> headache, memory loss, demyelination
Acute intermittent porhyria affected enzyme
Porphobilinogen deaminase
Acute intermittent porhyria - accumulated
Porphobilinogen
δ-ALA
coporphobilinogen (urine)
Acute intermittent porhyria symptoms
mnemonic - 5 Ps
- Painful abdomen
- Port wine - colored urine
- Polyneuropathy
- Psychological disturbances
- Precipitated by drugs (P450 inducers) Alcohol, starvation
Acute intermittent porhyria is precipitated by
- Drugs (cytochromic P-450 inducers)
- Alcohol
- Starvation
Acute intermittent porhyria treatment
Glucose and heme (inhibit ALA synthase)
Porphyria cutanea tarda affected enzyme
Uroporphyrinogen decarboxylase
Porphyria cutanea tarda - accumulated substrate
Uroporphyrin (tea colored urine)
Porphyria cutanea tarda - presenting symptoms
Blistering cutaneous photosensitivity
MC porphyria
Porphyria cutanea tarda
ALA synthase inhibitors
- heme
2. Glucose
Heme synthesis reaction - rate-limiting step
Where
Glycine + succinyl-CoA –> δ-aminolevuvulinic acid (δ-synthase + B6)
Mitochondria
δ-aminolevulinic acid dehydratase function
Affected by
Where
δ-ALA –> porphobilinogen
Inhibited by lead
Cytoplasm
Porphobilinogen deaminase function
Affected in
Where
Porphobilinogen –> hydroxymethylbilane
Affected in acute intermitend porphyria
Cytoplasm
Uroporphyrinogen decarboxylase function
Affected in
Where
Uroporphyrinogen III –> coproporphyrinogen III
Porphyria cutanea tarda
Cytoplasm
Ferrochelatase function
Where
Inhibited by
Protoporphyrin + iron –> heme
Mitochondria
Lead
Heme synthesis reactions
Glycine + succinyl coa +B6 –> δ-ALA –> porphobilinogen –> hydroxymethylbilane –> uroporphyrinogen III –> coproporphyrinogen III –> protoporphyrin + iron –> heme
δ-ALA synthase deficiency –>
sideroblastic anemia
