Iron is neat! Flashcards
What are hemes used in?
Cyt p450 and hemo/myoglobin
Hemoglobin is made of ______ globular subunits, the iron in the ring is in the ____________ state.
4, ferrous
Where does heme synthesis take place?
Phase I in mitochondria, II in cytosol, III in mitochondria
What is the rate limiting step in heme synthesis? What is it catalyzed by?
The rate limiting step is the conversion of glycine and succinyl-CoA to delta-aminolevulinic acid (ALA) by ALA synthase
What does ALA synthase require? What is it inhibited by?
PLP (B6), inhibited by heme and hemin
Acute intermittent porphyria is a problem in the _____________ enzyme and this process is related to __________ synthesis
Porphobilinogen deaminase (porphobilinogen -> hydroxymethylbilane) , hepatic
It is autosomal dominant
Congenital erythropoietic porphyria is an issue with the ___________________ enzyme and it is involved in what system?
Uroporphyrinogen III synthase (hydroxymethylbilane -> uroporphyrinogen III), erythocyte defect
It is autosomal recessive
What is the most common porphyria?
Porphyria cutanea tarda, problems with uroporphyrinogen decarboxylase (uroporphyrinogen III -> coproporhyrinogen III) and it is an issue in both hepatocytes and erythrocytes
It is autosomal dominant
Describe variegate porphyria
It is hepatic, defect in protoporphyrinogen oxidase (protoporphyrinogen IX -> protoporphyrin IX), the penultimate step in heme synth.
It is autosomal dominant
Lead affects what steps in heme synthesis?
- The last step, ferrochelatase (protoporphyrin IX-> heme)
2. First cytosolic step, ALA dehydratase (2 ALA -> porphobilinogen)
Drug related porphyria affects what step?
The last step, ferrochelatase (protoporphyrin IX -> heme)
What tint are urine and feces in most porphyria?
Dark
How often are RBC recycled?
Every 120 days
What does hemoglobin breakdown yield?
Globin -> AA, heme->degraded
Conjugated bilirubin contains bilirubin and what?
UDP glucuronic acid
Jaundice is caused by an abundance of _____________ bound to _________________ in the blood
Bilirubin and albumin
What are the final breakdown products of hemes? Where are they excreted?
Urobilin (yellow color of urine), stercobilin (red-brown color of feces)
During heme breakdown, iron is taken from the ____________ (__+) state to the _______________ (__+) state.
Ferrous, 2, ferric, 3
Heme oxygenase 1 is inducible by Nrf2, which is ubiquitinated and destroyed when not active much like what protein in epithelial architecture?
Beta-care in
In the small intestine, microbes concert bilirubin to colorless _____________
Urobilinogen
What are the three types of jaundice?
Pre-hepatic, intra-hepatic, post-hepatic
CC: Direct and indirect Bilirubin
Unconjugated bilirubin is insoluble in the blood
Conjugated (to glucuronate) bilirubin is soluble
Congenital Erythropoietic porphyria
Results from a deficiency of uroporphyrinogen III cosynthase
Key intermediates are diverted to the nonfunctional uroporphyrinogen I isomer that produces red color in ruin, teeth, premature destruction of erythrocytes and skin sensitivity
Color changes in bruises
Cleanup of the pooling of blood typical of a bruise by macrophages leads to degradation of hemoglobin to heme (red), biliverdin (green), and bilirubin (reddish yellow)
Formation of these degradation products manifests as visible color change of bruise
