Heme Synthesis, Porphyria, Lead Poisonong Flashcards Preview

Hematology And Oncology > Heme Synthesis, Porphyria, Lead Poisonong > Flashcards

Flashcards in Heme Synthesis, Porphyria, Lead Poisonong Deck (22):
1

Porphyrias?

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

2

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

3

Lead poisoning - enzyme affected (and where)

1. Ferrochelatase (mit)
2. ALA dehydratase (cytoplasm)

4

Lead poisoning - accumulation substrates

Protoporphyrin, δ-ALA (blood)

5

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

6

Acute intermittent porhyria affected enzyme

Porphobilinogen deaminase

7

Acute intermittent porhyria - accumulated

Porphobilinogen
δ-ALA
coporphobilinogen (urine)

8

Acute intermittent porhyria symptoms

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

9

Acute intermittent porhyria is precipitated by

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

10

Acute intermittent porhyria treatment

Glucose and heme (inhibit ALA synthase)

11

Porphyria cutanea tarda affected enzyme

Uroporphyrinogen decarboxylase

12

Porphyria cutanea tarda - accumulated substrate

Uroporphyrin (tea colored urine)

13

Porphyria cutanea tarda - presenting symptoms

Blistering cutaneous photosensitivity

14

MC porphyria

Porphyria cutanea tarda

15

ALA synthase inhibitors

1. heme
2. Glucose

16

Heme synthesis reaction - rate-limiting step
Where

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

17

δ-aminolevulinic acid dehydratase function
Affected by
Where

δ-ALA --> porphobilinogen
Inhibited by lead
Cytoplasm

18

Porphobilinogen deaminase function
Affected in
Where

Porphobilinogen --> hydroxymethylbilane
Affected in acute intermitend porphyria
Cytoplasm

19

Uroporphyrinogen decarboxylase function
Affected in
Where

Uroporphyrinogen III --> coproporphyrinogen III
Porphyria cutanea tarda
Cytoplasm

20

Ferrochelatase function
Where
Inhibited by

Protoporphyrin + iron --> heme
Mitochondria
Lead

21

Heme synthesis reactions

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

22

δ-ALA synthase deficiency -->

sideroblastic anemia