Metabolism XII: Heme Metabolism

Question 1

Describe the fate of the constituents of Hb.

Answer 1

• globin: converted into free amino acids
• iron: reutilized
• porphyrin: degraded into bilirubin

Question 2

A name for the genetic diseases resulting from abnormalities of the enzymes of heme biosynthesis:

Answer 2

porphyrias

Question 3

How is unconjugated bilirubin carried in the plasma?

Answer 3

it is carried as a complex with albumin, then delivered to the liver to be taken up by active transport and conjugated

Question 4

In which tissues is heme biosynthesis the highest?

Answer 4

bone marrow (for incorporation into Hb) and liver (for incorporation into cytochromes); however, note that heme is synthesized in virtually all mammalian tissues

Question 5

What are the general structural features of heme?

Answer 5

• Fe2+ atom in the center, which coordinates with all nitrogen atoms
• 4 pyrrole rings that contribute the central nitrogen atoms
• alternating side chains of acetic acid and propionic acid coming off of pyrrole rings

Question 6

Which two simple molecules contribute all of the atoms for the organic portion of heme?

Answer 6

??

Question 7

What is the first step in heme biosynthesis?

Answer 7

succinyl CoA + glycine –> ALA (enzyme=ALA synthase)

*this is the RLS and regulated step, and it occurs in the mitochondria

Question 8

What are the differences b/t porphyrinogen intermediates porphyrins? Can porphyrinogens be non-enzymatically converted to porphyrins?

Answer 8

• porphyrinogens have NO double bonds at the bridging carbons and are colorLESS
• porphyrins DO have double bonds at the bridging carbons, and they are colored and highly fluorescent
• porphyrinogens CAN be non-enzymatically converted to porphyrins via oxidation by light

Question 9

How is heme biosynthesis regulated in the liver?

Answer 9

heme inhibits its own synthesis by decreasing the activity of ALAS1