"Molecular & Cellular Princ Med Heme Degradation Mark Schmitt" GABY

Question 1

What is the lifetime of a red blood cell?

Answer 1

120 days

Question 2

What is the major protein in red blood cells?

Answer 2

Hemoglobin

Question 3

Removal of aging red blood cells occurs predominantly in the ___

Answer 3

spleen

*The liver and bone marrow are capable of removing senescent erythrocytes from the circulation, but these play a secondary role

Question 4

The spleen has a class of cells called ___ cells that can engulf a red-blood cell through ___

Answer 4

reticular endothelial; phagocytosis

Question 5

What is another name for the reticular endothelial cells?

Answer 5

Mononuclear phagocytes

*they also play a role in immunity

Question 6

What carrier proteins are available to bind hemoglobin or free heme in order to prevent the loss of iron via the kidney that could otherwise occur in the event that red cell destruction occurs at a site other than the spleen or liver?

Answer 6

(1) Haptoglobin - binds methemoglobin dimers (hemoglobin with the iron in the ferric state)
(2) Hemepexin - binds free heme
(3) Transferrin - binds free iron

Question 7

In heme degradation: globin is ___ to free amino acids; released iron is ___

Answer 7

hydrolyzed; recycled

Question 8

Fill in the product and enzyme that catalyzes the reaction below, and reaction location:

Answer 8

Product: Biliverdin

Enzyme: Heme oxygenase

Location: spleen, endoplasmic reticulum

Question 9

Fill in the product and enzyme that catalyzes the reaction below, and reaction location:

Biliverdin … (hint: reduction)

Answer 9

Product: Bilirubin

Enzyme: Biliverdin reductase

Location: spleen

Question 10

Fill in the product and enzyme that catalyzes the reaction below, and reaction location:

Bilirubin … (hint: conjugation)

Answer 10

Product: Bilirubin Diglucuronide (conjugated)

Enzyme: Glucuronyl bilirubin transferase

Location: Liver, endoplasmic reticulum

Question 11

Is bilirubin water soluble?

Answer 11

NO

*it is made water soluble by attachment of two sugar groups to the propionate side chains

Question 12

Crigler-Najjar syndrome

Answer 12

Due to a deficiency in UDP-glucuronyl transferase and results in severe jaundice

Question 13

Neonatal jaundice

Answer 13

Temporary condition due to the production of insufficient levels of UDP-glucuronyl transferase by the infant

(a) Phototherapy- Irradiation of jaundiced infants with fluorescent lights
(b) Irradiated bilirubin breakdown products are more soluble than bilirubin and can be excreted by the liver into the bile without conjugation to glucuronic acid

Question 14

What is the fate of conjugated bilirubin?

Answer 14

Liver –> bile canaliculi –> gall bladder –> intestinal tract

*Intestinal bacteria convert conjugated bilirubin to a series of urobilinogens and related products

Question 15

Urobilinogen

Answer 15

colorless

Oxidation leads to the formation of urobilin, which contributes to the color of normal urine and feces

Question 16

Jaundice

Answer 16

abnormalities in bilirubin metabolism

Question 17

Prehepatic jaundice

Answer 17

Massive breakdown of red blood cells resulting in overproduction of free bilirubin

The liver cells cannot conjugate bilirubin at the rate it enters the liver, hence you get a build-up of unconjugated bilirubin in the blood

Question 18

Hepatic jaundice

Answer 18

Diseased condition of the liver (e.g. hepatitis, cirrhosis) that prevents uptake or conjugation of bilirubin

Question 19

Posthepatic jaundice

Answer 19

Blockage of bile flow out of the liver and into the intestinal tract, build-up of conjugated bilirubin

Question 20

Bilirubin is considered a major ___ in the blood for scavenging free radicals

Answer 20

anti-oxidant

Question 21

What happens to iron during heme degradation?

Answer 21

It is stored in ferritin and hemosiderin (degraded form of ferritin)

Question 22

An increase in iron entering tissues results in an ___ in ferritin content

Answer 22

increase

Question 23

What does transferrin do for iron?

Answer 23

It transports it from the spleen (where RBCs are degraded) back to the marrow (where RBCs are synthesized)

Question 24

Ferro-transferrin binds a receptor on the cell membrane at pH ___

Answer 24

7

Question 25

Ferro- transferrin and its receptor are taken up by ___ in clathrin coated pits

Answer 25

endocytosis

Question 26

The pH in the vesicle carrying ferro- transferrin and its receptor is lowered to pH ___ causing the dissociation of iron from transferrin

Answer 26

5

Question 27

Receptor and apotransferrin are returned to the plasma membrane where the pH is ___ and the
transferrin will no longer bind its receptor

Answer 27

7

Question 28

A 52-year old man was admitted to the hospital with a yellow discoloration of the skin and sclera. He had no abdominal pain but had pale stools. His liver function tests showed: high conjugated bilirubin (13.5mg/dl, normal

Answer 28

A. pancreatic cancer.

Question 29

A patient checks into the ER looking yellow and feeling very ill. A blood test is ordered and A a van den Bergh reaction is performed. The test reveals a high level of conjugated bilirubin.
The diagnosis might include:

A. Posthepatic jaundice.
B. Hepatic jaundice.
C. Prehepatic jaundice.
D. Hepatic porphyria.
E. Lesch-Nyhan syndrome.

Answer 29

A. Posthepatic jaundice.

Question 30

All of the following are true about biliverdin except:

A. It is an important antioxidant in the body.
B. It is conjugated with glucuronic acid in the liver and secreted into the bile.
C. It is generated along with carbon monoxide by heme oxidase.
D. It is generated mainly in the spleen.
E. All of the above are true.

Answer 30

A. It is an important antioxidant in the body.
AND
B. It is conjugated with glucuronic acid in the liver and secreted into the bile.

Question 31

All of the following are true about jaundice except:

A. it is a yellow discoloration of the skin and sclerae.
B. it is caused by a build-up of bilirubin in the plasma.
C. it often occurs in newborn infants.
D. it can be caused by pancreatic cancer.
E. it can be caused by kidney failure.

Answer 31

E. it can be caused by kidney failure.

Question 32

Apo-transferrin:

A. is the major storage molecule for iron in a cell.
B. binds to its receptor at neutral pH.
C. is made by the liver.
D. is degraded in the lysosome.
E. has four bound iron atoms.

Answer 32

C. is made by the liver.

Question 33

Bilirubin is conjugated to glycuronic acid:

A. to make it more water soluble.
B. so it can be transported to the liver.
C. to help feed the bacteria in our gut.
D. by the enzyme bilirubin reductase.
E. before the liver resynthesizes heme from it.

Answer 33

A. to make it more water soluble.

Question 34

Blockage of the biliary duct:

A. can lead to a build up of conjugated bilirubin in the body.
B. is characterized by a high level of biliverdin in the blood.
C. can be fatal due to a failure to be able to recycle iron.
D. would cause a patient’s feces to become dark brown.
E. leads to failure to internalize apotransferrin since it has no iron to bind.

Answer 34

A. can lead to a build up of conjugated bilirubin in the body.

Question 35

In heme degradation:

A. all of the components are recycled.
B. the heme is saved for reincorporation into hemoglobin.
C. carbon monoxide is produced.
D. bilirubin is deconjugated in the liver.
E. ADP-glucuronic acid is used.

Answer 35

C. carbon monoxide is produced.

Question 36

The enzyme glucuronyl bilirubin transferase is deficient in:

A. Hartnup's disease.
B. lead poisoning.
C. congenital erythropoietic porphyria.
D. Lesch-Nyhan syndrome.
E. Crigler-Najjar syndrome.

Answer 36

E. Crigler-Najjar syndrome.

Question 37

The first step of heme degradation by heme oxygenase
A. uses NADPH as a cofactor.
B. requires O2.
C. produces CO as a byproduct.
D. both A and C.
E. All of the above.

Answer 37

E. All of the above.

Question 38

Transferrin:

A. holds four iron atoms. -
B. binds iron with low affinity at neutral pH.
C. is made in the spleen.
D. binds the LDL receptor.
E. undergoes receptor mediated endocytosis.

Answer 38

E. undergoes receptor mediated endocytosis.

Question 39

Which of the following is false:

A. Transferrin is a protein specialized for the transport of iron
B. Transferrin is a glycoprotein synthesized in the liver that is plasma located.
C. Transferrin and its receptor are recycled.
D. Transferrin binds iron at low and neutral pH but not high pH.
E. Apotransferrin will not bind its receptor at neutral pH.

Answer 39

D. Transferrin binds iron at low and neutral pH but not high pH.