Heme

Question 1

Where is heme synthesis the highest?

Answer 1

In the bone marrow (for erythropoiesis) and in the liver (for cytochrome formation)

Question 2

What are the most striking features of heme?

Answer 2

There is an iron ion in the middle surrounded by four interconnected pyrrole rings

Question 3

Step one of heme synthesis

Answer 3

Succinyl CoA and glycine are combined to form delta-aminolevulinic acid

Question 4

What catalyzes the first step in heme synthesis?

Answer 4

ALA synthase

Question 5

What are differences between porphyrinogens and porphyrins?

Answer 5

Porphyrinogens: no double bonds at bridges, colorless
Porphyrins: double-bonded at bridges, colored, fluorescent, and photodegradable

Question 6

How do porphyrinogens get non-enzymatically oxidized?

Answer 6

Become porphyrins in response to light

Question 7

How is heme biosynthesis regulated in the liver?

Answer 7

Feedback inhibition by heme on ALA synthase

Question 8

What are the cells primarily responsible for the degradation of hemoglobin?

Answer 8

Reticuloendothelial system

Question 9

What are the fates of globin, iron, and porphyrin after degradation of heme?

Answer 9

Globin: broken down into free amino acids
Iron: recycled
Porphyrin: excreted as bile

Question 10

Heme oxygenase

Answer 10

Breaks down porphyrin into biliverdin

Question 11

Biliverdin reductase

Answer 11

Reduces biliverdin to bilirubin IX-alpha (indirect bilirubin/unconjugated bilirubin)

Question 12

How is unconjugated bilirubin carried in the plasma?

Answer 12

As a complex with albumin

Question 13

How is the albumin-bilirubin complex taken up by the liver?

Answer 13

Through active transport

Question 14

Describe the process of conjugation of bilirubin in the liver

Answer 14

Glucuronic acid x2 are attached to the unconjugated bilirubin by the propionic side chains

Question 15

What enzyme catalyzes the reaction of bilirubin conjugation?

Answer 15

Bilirubin UDP glucuronyltransferase

Question 16

What happens to bilirubin after conjugation?

Answer 16

It is actively secreted into the bile canaliculi

Question 17

Definition of hyperbilirubinemia

Answer 17

High blood levels of bilirubin (>1 mg/dL)

Question 18

Definition of jaundice

Answer 18

Diffusion of bilirubin into tissues, making them appear yellow (detectable at serum levels of 2-2.5 mg/dL)

Question 19

Clinical consequences of hyperbilirubinemia

Answer 19

At concentrations above 25 mg/dL, albumin’s carrying capacity is reached and free unconjugated bilirubin is present in the blood, which can cross the BBB and cause severe central nervous system damage

Question 20

Hemolysis

Answer 20

Destruction of erythrocytes; causes increase in unconjugated bilirubin

Question 21

Biliary obstruction

Answer 21

Conjugated bilirubin is not transported back to the liver, and instead spills into blood, causing hyperbilirubinemia. Also causes dark urine and chalky, white stools.

Question 22

Hepatitis and liver cirrhosis

Answer 22

Decreased conjugation and excretion of bilirubin, causing increase in both conjugated and unconjugated bilirubin.

Question 23

Neonatal jaundice

Answer 23

Fragile erythrocytes. Decreased conjugation, excretion, and uptake of bilirubin. Causes increase in unconjugated bilirubin.

Question 24

What is a treatment for neonatal jaundice?

Answer 24

Phototherapy