Heme biosyn and porphyrias Flashcards
What are the major sites of heme synthesis?
Erythrocytes of the bone marrow and the liver
What are porphyrins?
Cyclic compounds that readily bind metal ions, particularly iron (Fe)
What is the opening step in the pathway of porphyrin biosynthesis? (It’s also the rate limiting step!)
Glycine and succinyl CoA combine to form ALA; requires ALA synthase and PLP
What is the next step (2nd overall) after ALA is formed?
ALA is then dehydrated to form porphobilinogen.
What is the next step after porphobilinogen is formed?
4 molecules of porphobilinogen are then condensated to form uroporphyrinogen III
What is the next step after uroporphyrinogen III?
It is converted to heme, after a series of conversions.
Individuals in which an enzyme deficiency leads to accumulation of tetra pyrrole intermediates are ____
photosensitive
What porphyrias occur in the liver? In the erythrocytes?
Liver: varigate, hereditary coproporphyria, acute intermittent, porphyria cutanea tarda
Erythrocytes: congenital erythropoetic, erythropoetic protoporphyria, porphyria cutanea tarda
In which porphyria is patients NOT photosensitive?
Acute intermittent porphyria; urine darkens on exposure to light and air
Porphyria cutanea tarda characteristics?
- Chronic and most common porphyria
- Deficiency of uroporphyringogen decarboxylase
- Urine is red-brown, patient develops photosensitivity
The activity of what enzyme is increased, in porphyrias?
- Synthesis of cytochrome P450 increases, lowering intracellular heme levels
- ALA synthase activity increases, due to lowered intracellular heme concentrations
Why is glucose and insulin used, as tx for acute porphyrias?
- An increase in insulin or glucose in the blood inhibits PGC-1 alpha
- PGC-1 alpha increases ALA synthase, which increases heme production
- If heme cannot be produced (as quickly), it cannot build up and therefore, porphyrias cannot occur.
What is the tx for porphyrias? IV injection of ____
Hemin
