L04: Heme Metabolism Part 2

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