Review 10: Heme Metabolism

Question 1

Where is the biggest site of heme biosynthesis in the body?

Answer 1

1) bone marrow (for incorporation into hemoglobin)

2) liver (incorporation into cytochromes)

Question 2

Define porphyria

Answer 2

genetic diseases resulting from abnormalities of enzymes of heme biosynthesis

Question 3

Catabolism of heme produces ____________

Answer 3

bilirubin

Question 4

What organ takes up bilirubin, conjugates it, and secretes it into bile?

Answer 4

the liver

Question 5

What is the rate limiting step in heme biosynthesis?

Answer 5

Step 1 (succinyl coA + glycine ——> ALA) occurs in the mitochondria

Question 6

Where in the cell does heme biosynthesis occur?

Answer 6

Steps 1, 6, 7, 8 –> mitochondria

Steps 2, 3, 4, 5 –> cytosol

Question 7

What is the defining characteristic of porphyrinogen?

Answer 7

NO double bonds at bridging carbons (colorless)

Question 8

What is the defining characteristics or porphyrins?

Answer 8

double bonds at bridging carbons (COLORED)

Question 9

True or false: there is only one ALA synthase for both the liver and the bone marrow

Answer 9

FALSE (different enzymes under different regulation)

Question 10

Which ALA synthase is regulated by heme?

Answer 10

ALAS1 in the liver

Question 11

What is responsible for causing symptoms in porphyrias?

Answer 11

increase in metabolic intermediates (not a decrease in heme production)

Question 12

What are 2 types of porphyria?

Answer 12

1) acute intermittent (deficiency of porphobilinogen deaminase leading to a build up of porphobilinogen)
2) variegate (cutaneous) (deficiency of

both have reduced heme synthesis

Question 13

What does lead poisoning do to the body?

Answer 13

inhibit 3 important enzymes in the heme biosynthetic pathway

Question 14

What is half life of RBCs?

Answer 14

120 days

Question 15

Unconjugated bilirubin is carried in the plasma as a complex with _________

Answer 15

albumin (delivered to the liver)

Question 16

How is unconjugated bilirubin conjugated in the liver?

Answer 16

2 glucuronic acid groups (from UDP-glucuronate) are attached to unconjugated bilirubin via propionic acid side chains

Question 17

Where is bilirubin diglucuronide deconjugated?

Answer 17

the intestine by bacterial flora

oxidized to stercobilins which give stool its color

Question 18

What compound gives urine its color?

Answer 18

urobilin

Question 19

What is the cut off for classifying hyperbilirubinemia?

Answer 19

> 1mg/dL

Question 20

True or False: hyperbilirubinemia only counts the conjugated form

Answer 20

FALSE; can be either the conjugated or unconjugated form

Question 21

What is responsible for the yellowing color in jaundice?

Answer 21

elevated bilirubin diffusing into tissues (detectable in sclera when bilirubin reaches 2-2.5mg/dL)

Question 22

Why is hyperbilirubinemia dangerous?

Answer 22

Conjugated form: benign
Unconjugated form: benign when bound to albumin (<25mg/dL) but above that when it is free, it can enter the brain and cause toxic encephalopathy

Question 23

What are some causes of jaundice?

Answer 23

1) Hemolysis (increase in unconjugated bilirubin)
2) Biliary obstruction (conjugated spills over into blood – dark urine and chalky white feces)
3) hepatitis/cirrhosis (decreased conjugation of bilirubin)
4) Neonatal physiological jaundice – immature hepatic system (increase in unconjugated bilirubin)

Question 24

Why are jaundice babies treated with UV light?

Answer 24

blue light can convert the insoluble, BBB permeable unconjugated bilirubin into isomers that are more soluble