Porphyrias Flashcards
Where does heme synthesis begin, and with what precursors?
Mitochondria.
Glycine + succinyl-CoA (+B6)
What is the rate limiting step of heme synthesis, what enzyme?
glycine + succinyl CoA to Delta-Aminolevulinic Acid.
Enzyme: Aminolevulinic Acid Synthase (ALAS).
What is the result of a genetic defect in ALAS?
Sideroblastic anemia. X-linked.
What happens to Delta-Aminolevulinic Acid?
Goes to cytoplasm, is converted to porphobilinogen by ALAD (dehyratase).
What can inhibit ALAD?
Lead poisoning.
What happens to porphobilinogen?
Converted to Hydroxymethylbilane by Porphobilinogen deaminase.
What is the result of a deficiency in porphobilinogen deaminase?
Acute intermittent porphyria.
What happens to hydroxymethylbilane?
Gets converted to uroporphyrinogen III through a bunch of steps.
What happens to uroporphyrinogen III?
Gets converted to coproporhyrinogen III by uroporphyinogen decarboxylase.
What does a deficiency of uroporphyinogen decarboxylase cause?
Porphyria cutanea tarda.
What happens to coproporhyrinogen III?
Goes into mito, becomes protoporphyrin, then ferrochelatase combines it with Fe –> Heme.
What can inhibit ferrochelatase?
Lead poisoning.
Review, what are the steps of heme synthesis?
Glyc + succ –> D-ALA –> Porphobilinogen –> Hydroxymethybilane –> Uroporphyrinogen –> Coproporphyinogen –> Protoporphyrin -> Heme.
What are the affected enzymes in lead poisoning?
ALAD and Ferrochelatase.
What are the accumulated substrates in lead poisoning?
protoporphyrin, D-ALA (blood).
How can children be exposed to lead?
Lead paint.
What is the presentation of lead poisoning in children?
Mentral deterioration.
How can adults be exposed to lead?
Environmental - batteries, ammunition.
What are the sx of lead poisoning in adults?
Abdominal pain, blue line at gums, peripheral neuropathy, urine darkens upon standing in sunlight, headache, memory loss.
What is the affected enzyme in acute intermittent porphyria?
Porphobilinogen deaminase
What are the accumulated substances in AIP?
Porphobilinogen, D-ALA, Co-porphobilinogen (urine).
What are the sx of AIP?
Painful abdomen, Port-wine colored urine, Polyneuropathy, Psychological disturbances, Pre-cip by drugs.
What can precipitate AIP?
CP450 inducers, alcohol, starvation.
What is the treatment for AIP?
Glucose and heme inhibit ALAS.
