Heme Synthesis, Porphyria, Lead Poisonong

Question 1

Porphyrias?

Answer 1

Hereditary or acquired conditions of defective heme synthesis that lead to the accumulation of heme precursors (lead poisoning is a similar condition)

Question 2

Heme synthesis reactions and enzymes (and where)

Answer 2

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

Question 3

Lead poisoning - enzyme affected (and where)

Answer 3

1. Ferrochelatase (mit)

2. ALA dehydratase (cytoplasm)

Question 4

Lead poisoning - accumulation substrates

Answer 4

Protoporphyrin, δ-ALA (blood)

Question 5

Lead poisoning - way of exposure and neurological symptoms (children and adults)

Answer 5

Children –> exposure to lead paint –> mental deterioration
Adults –> environmental exposure (batteries ammunition) –> headache, memory loss, demyelination

Question 6

Acute intermittent porhyria affected enzyme

Answer 6

Porphobilinogen deaminase

Question 7

Acute intermittent porhyria - accumulated

Answer 7

Porphobilinogen
δ-ALA
coporphobilinogen (urine)

Question 8

Acute intermittent porhyria symptoms

Answer 8

mnemonic - 5 Ps

1. Painful abdomen
2. Port wine - colored urine
3. Polyneuropathy
4. Psychological disturbances
5. Precipitated by drugs (P450 inducers) Alcohol, starvation

Question 9

Acute intermittent porhyria is precipitated by

Answer 9

1. Drugs (cytochromic P-450 inducers)
2. Alcohol
3. Starvation

Question 10

Acute intermittent porhyria treatment

Answer 10

Glucose and heme (inhibit ALA synthase)

Question 11

Porphyria cutanea tarda affected enzyme

Answer 11

Uroporphyrinogen decarboxylase

Question 12

Porphyria cutanea tarda - accumulated substrate

Answer 12

Uroporphyrin (tea colored urine)

Question 13

Porphyria cutanea tarda - presenting symptoms

Answer 13

Blistering cutaneous photosensitivity

Question 14

MC porphyria

Answer 14

Porphyria cutanea tarda

Question 15

ALA synthase inhibitors

Answer 15

1. heme

2. Glucose

Question 16

Heme synthesis reaction - rate-limiting step

Where

Answer 16

Glycine + succinyl-CoA –> δ-aminolevuvulinic acid (δ-synthase + B6)
Mitochondria

Question 17

δ-aminolevulinic acid dehydratase function
Affected by
Where

Answer 17

δ-ALA –> porphobilinogen
Inhibited by lead
Cytoplasm

Question 18

Porphobilinogen deaminase function
Affected in
Where

Answer 18

Porphobilinogen –> hydroxymethylbilane
Affected in acute intermitend porphyria
Cytoplasm

Question 19

Uroporphyrinogen decarboxylase function
Affected in
Where

Answer 19

Uroporphyrinogen III –> coproporphyrinogen III
Porphyria cutanea tarda
Cytoplasm

Question 20

Ferrochelatase function
Where
Inhibited by

Answer 20

Protoporphyrin + iron –> heme
Mitochondria
Lead

Question 21

Heme synthesis reactions

Answer 21

Glycine + succinyl coa +B6 –> δ-ALA –> porphobilinogen –> hydroxymethylbilane –> uroporphyrinogen III –> coproporphyrinogen III –> protoporphyrin + iron –> heme

Question 22

δ-ALA synthase deficiency –>

Answer 22

sideroblastic anemia