Flashcards in Heme Catabolism Deck (21)
What are the 2 goals of heme catabolism?
1)handle the hydrophobic products of porphyrin ring cleavage
2)retain, safely mobilize & reuse iron
What 2 reactions can heme/Fe2+ perform under oxidative stress?
Fe2+ can generate ROS and cause lipid peroxidation
Heme is hydrophobic and can intercalate into lipid bilayers
What are the effects of lipid peroxidation?
structural changes in membranes
adduct/crosslink formation with non lipids
disruptions in membrane dependent signaling
What molecule does free hemoglobin scavenge?
NO, if too much is bound vasoconstriction can occur...leads to HTN
Which route of hemolysis is hte major route?
Types of macrophages
extravascular: tissue macrophages of red pulp of spleen and kupfer cells in liver
intravascular: CD163 positive macrophages that scavenge hemoglobin-haptoglobin complex
glycoprotein that binds free Hb
produced by liver in hepatocytes
levels increase during inflammation and neoplastic disease
What happens to haptoglobin during hemolysis?
Can haptoglobin-hemoglobin pass through glomerular filter?
No, this helps conserve iron
What happens when haptoglobin is overwhelmed?
Hb converts to metHb which liberates heme
ferriheme binds albumin and other things where it is transferred to hemopexin
glycoprotein that binds free heme
produced by liver
increased levels during heme overload
What receptor binds the hemopexin-heme complex?
CD91 scavenger receptor
Once heme is taken up by a macrophage what happens?
globin protein is degraded in lysosome
heme is transferred to cytosol and catabolized by heme oxygenase 1 (HO-1)
What occurs with the accumulation of bilirubin?
jaundice or icterus
What do inherited disorders of bilirubin metabolism lead to?
What color is bilirubin?
How is heme ring opened in macrophage?
1)ring is cleaved by HO-1 this requires electrons from CYPOR
2)oxidation by molecular oxygen with elimination of CO and release of iron, resulting in biliverdin
What color is biliverdin?
How is biliverdin converted to bilirubin?
by biliverdin reductase
What happens to bilirubin that crosses into the bloodstream?
it is bound to albumin