Heme Synthesis Flashcards
Where does heme synthesis occur (tissue)?
bone marrow
Where are cytochromes synthesizes (tissue)?
liver
What is the regulated step of heme synthesis? Where is this located?
succinyl-CoA + Glycine»ALA
Enzyme: aminolevulinine acid synthase (ALA synthase)
Location: mitochondria
**ALA is exported out to the cytoplasm for next reaction
Between porphobilinogen and uroporphyrinogen, which is photoactive?
uroporphyrinogen (from UPG synthase III)
How is heme synthesis inhibited?
end-product inhibition
How is heme synthesis stimulated?
increased demand for heme (ie heme-containing enzymes such as cytochrome P450)
In what organelle does heme get its iron insertion?
mitochondria
What’s the downside to heme regulation, especially when there’s a disorder?
If the end product is not made, the pathway doesn’t stop
- deficiency in porphobilinogen deaminase
- PBG accumulates and gives urine dark red color
acute intermittent porphyria (AIP)
- intermittent because it’s only bad when heme synthesis is occuring
- deficiency in uroporhyrinogen decarboxylase
- absorbs UV light (after the photoactive product has been made), urine turns pink fluorescence
- buildup of porphyrins
- causes photosensitivity of the skin and leads to blistering of sun-exposed areas
PCT - Porphyria cutanea tarda
- inhibitor of PBG synthase (cytosol) and ferrochlatase (mitochondria)
- accumulation of ALA and other heme precursors
- symptoms are similar to porphyria
lead poisoning
What reducing equivalent is required for heme degradation?
NADPH
Where does heme degradation occur?
spleen
Majority of bilirubin exits which route?
intestines as feces
Which organ needs to remain bilirubin-free?
brain
