Porphyrias

Question 1

Where does heme synthesis begin, and with what precursors?

Answer 1

Mitochondria.

Glycine + succinyl-CoA (+B6)

Question 2

What is the rate limiting step of heme synthesis, what enzyme?

Answer 2

glycine + succinyl CoA to Delta-Aminolevulinic Acid.

Enzyme: Aminolevulinic Acid Synthase (ALAS).

Question 3

What is the result of a genetic defect in ALAS?

Answer 3

Sideroblastic anemia. X-linked.

Question 4

What happens to Delta-Aminolevulinic Acid?

Answer 4

Goes to cytoplasm, is converted to porphobilinogen by ALAD (dehyratase).

Question 5

What can inhibit ALAD?

Answer 5

Lead poisoning.

Question 6

What happens to porphobilinogen?

Answer 6

Converted to Hydroxymethylbilane by Porphobilinogen deaminase.

Question 7

What is the result of a deficiency in porphobilinogen deaminase?

Answer 7

Acute intermittent porphyria.

Question 8

What happens to hydroxymethylbilane?

Answer 8

Gets converted to uroporphyrinogen III through a bunch of steps.

Question 9

What happens to uroporphyrinogen III?

Answer 9

Gets converted to coproporhyrinogen III by uroporphyinogen decarboxylase.

Question 10

What does a deficiency of uroporphyinogen decarboxylase cause?

Answer 10

Porphyria cutanea tarda.

Question 11

What happens to coproporhyrinogen III?

Answer 11

Goes into mito, becomes protoporphyrin, then ferrochelatase combines it with Fe –> Heme.

Question 12

What can inhibit ferrochelatase?

Answer 12

Lead poisoning.

Question 13

Review, what are the steps of heme synthesis?

Answer 13

Glyc + succ –> D-ALA –> Porphobilinogen –> Hydroxymethybilane –> Uroporphyrinogen –> Coproporphyinogen –> Protoporphyrin -> Heme.

Question 14

What are the affected enzymes in lead poisoning?

Answer 14

ALAD and Ferrochelatase.

Question 15

What are the accumulated substrates in lead poisoning?

Answer 15

protoporphyrin, D-ALA (blood).

Question 16

How can children be exposed to lead?

Answer 16

Lead paint.

Question 17

What is the presentation of lead poisoning in children?

Answer 17

Mentral deterioration.

Question 18

How can adults be exposed to lead?

Answer 18

Environmental - batteries, ammunition.

Question 19

What are the sx of lead poisoning in adults?

Answer 19

Abdominal pain, blue line at gums, peripheral neuropathy, urine darkens upon standing in sunlight, headache, memory loss.

Question 20

What is the affected enzyme in acute intermittent porphyria?

Answer 20

Porphobilinogen deaminase

Question 21

What are the accumulated substances in AIP?

Answer 21

Porphobilinogen, D-ALA, Co-porphobilinogen (urine).

Question 22

What are the sx of AIP?

Answer 22

Painful abdomen, Port-wine colored urine, Polyneuropathy, Psychological disturbances, Pre-cip by drugs.

Question 23

What can precipitate AIP?

Answer 23

CP450 inducers, alcohol, starvation.

Question 24

What is the treatment for AIP?

Answer 24

Glucose and heme inhibit ALAS.

Question 25

What is the deficiency in porphyria cutanea tarda?

Answer 25

Uroporphyrinogen decarboxylase.

Question 26

What is the accumulated substance in PCT?

Answer 26

Uroporphyrin (tea colored urine).

Question 27

What are the presenting sx of PCT?

Answer 27

Blistering cutaneous photosensitivity.

Question 28

Which is the most common porphyria?

Answer 28

PCT.

Question 29

What can cause PCT?

Answer 29

Congenital.

Aquired - aromatic hydrocarbons, estrogen supplementation, or hepatitis C.