L04: Heme Metabolism Part 2

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30 Terms

1
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Tightly bound prosthetic group of hemoglobin?

heme

2
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Are heme proteins colored or uncolored? Why?

colored

-conjugated/alternating double bonds

3
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How is a majority of the human body's heme derived?

endogenous synthesis

4
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Important intermediate of heme synthesis?

porphyrinogens

5
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Do porphyrinogens absorb visible light?

no

6
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2 most important sites of heme synthesis?

bone marrow

liver

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What does the liver synthesize heme for?

cytochrome P450

8
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1st step of heme synthesis? (enzyme)

succinyl-coA + glycine -----------> Aminolevulinate (ALA)

enzyme: ALA synthase

9
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Committed/regulatory step of heme synthesis?

(Succinyl-coA + glycine ----------> aminolevulinate) (ALA)

enzyme: ALA synthase

10
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Vitamin needed for ALA synthase?

vitamin B6

11
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The 1st step of heme synthesis is done where?

mitochondria

12
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Feedback inhibitor of heme synthesis?

unbound heme

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2nd step of heme synthesis?

aminolevulinate --------> porphobilinogen

enzyme: ALA dehydratase

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3rd step of heme synthesis?

porphobilinogen ----------> uroporphyrinogen I + III

enzymes:
-Uroporphyrinogen I synthase
-Urophyrinogen III cosynthase

15
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The conversion from porphobilinogen to uroporphyrinogen is important because?

it requires a synthase and cosynthase to continue the pathway

16
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4th step of heme synthesis?

uroporphyrinogenn III -------> coprophyringogen III

enzyme: uroporphyrinogen decarboxylase 3

17
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5th step of heme synthesis?

coprophyrinogen III ----------> protophyrinogen IX

enzyme: coprophyrinogen oxidase

18
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6th step of heme synthesis?

protophyrinogen IX ---------> protophyrin IX

enzyme: protophyrinogen oxidase

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The last 3 steps of heme synthesis occur where?

mitochondria

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Where is heme degraded to bilirubin?

spleen

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Heme to bilirubin pathway?

heme --------> biliverdin (heme oxygenase)

biliverdin -------> bilirubin (biliverdin reductase)

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How is bilirubin conjugated in the liver?

UDP-glucuronyl transferase to add UDP-glucuronic acid

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Heme to biliverdin requires?

O2 + coenzyme (NADPH)

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What is required to catalyze reaction from biliverdin to bilirubin?

coenzyme (NADPH)

25
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How does unconjugated bilirubin get across liver?

facilitated diffusion

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In the intestine, what converts bilirubin to urobilinogen?

bacteria

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What transports conjugated bilirubin from liver to bile? Where? Is it ATP-dependent?

ATP-dependent multi drug resistance protein 2 in the periportal hepatocytes

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What is used to transport some conjugated bilirubin to the perivenous hepatocytes?

Multidrug resistance protein 1, 3, 4

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How does conjugated bilirubin enter perivenous hepatocytes?

organic anion transporting polypeptides

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How is protophyrin IX converted into heme?

ferrochelatase