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Tightly bound prosthetic group of hemoglobin?
heme
Are heme proteins colored or uncolored? Why?
colored
-conjugated/alternating double bonds
How is a majority of the human body's heme derived?
endogenous synthesis
Important intermediate of heme synthesis?
porphyrinogens
Do porphyrinogens absorb visible light?
no
2 most important sites of heme synthesis?
bone marrow
liver
What does the liver synthesize heme for?
cytochrome P450
1st step of heme synthesis? (enzyme)
succinyl-coA + glycine -----------> Aminolevulinate (ALA)
enzyme: ALA synthase
Committed/regulatory step of heme synthesis?
(Succinyl-coA + glycine ----------> aminolevulinate) (ALA)
enzyme: ALA synthase
Vitamin needed for ALA synthase?
vitamin B6
The 1st step of heme synthesis is done where?
mitochondria
Feedback inhibitor of heme synthesis?
unbound heme
2nd step of heme synthesis?
aminolevulinate --------> porphobilinogen
enzyme: ALA dehydratase
3rd step of heme synthesis?
porphobilinogen ----------> uroporphyrinogen I + III
enzymes:
-Uroporphyrinogen I synthase
-Urophyrinogen III cosynthase
The conversion from porphobilinogen to uroporphyrinogen is important because?
it requires a synthase and cosynthase to continue the pathway
4th step of heme synthesis?
uroporphyrinogenn III -------> coprophyringogen III
enzyme: uroporphyrinogen decarboxylase 3
5th step of heme synthesis?
coprophyrinogen III ----------> protophyrinogen IX
enzyme: coprophyrinogen oxidase
6th step of heme synthesis?
protophyrinogen IX ---------> protophyrin IX
enzyme: protophyrinogen oxidase
The last 3 steps of heme synthesis occur where?
mitochondria
Where is heme degraded to bilirubin?
spleen
Heme to bilirubin pathway?
heme --------> biliverdin (heme oxygenase)
biliverdin -------> bilirubin (biliverdin reductase)
How is bilirubin conjugated in the liver?
UDP-glucuronyl transferase to add UDP-glucuronic acid
Heme to biliverdin requires?
O2 + coenzyme (NADPH)
What is required to catalyze reaction from biliverdin to bilirubin?
coenzyme (NADPH)
How does unconjugated bilirubin get across liver?
facilitated diffusion
In the intestine, what converts bilirubin to urobilinogen?
bacteria
What transports conjugated bilirubin from liver to bile? Where? Is it ATP-dependent?
ATP-dependent multi drug resistance protein 2 in the periportal hepatocytes
What is used to transport some conjugated bilirubin to the perivenous hepatocytes?
Multidrug resistance protein 1, 3, 4
How does conjugated bilirubin enter perivenous hepatocytes?
organic anion transporting polypeptides
How is protophyrin IX converted into heme?
ferrochelatase