"Molecular & Cellular Princ Med Heme Degradation Mark Schmitt" GABY Flashcards
What is the lifetime of a red blood cell?
120 days
What is the major protein in red blood cells?
Hemoglobin
Removal of aging red blood cells occurs predominantly in the ___
spleen
*The liver and bone marrow are capable of removing senescent erythrocytes from the circulation, but these play a secondary role
The spleen has a class of cells called ___ cells that can engulf a red-blood cell through ___
reticular endothelial; phagocytosis
What is another name for the reticular endothelial cells?
Mononuclear phagocytes
*they also play a role in immunity
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?
(1) Haptoglobin - binds methemoglobin dimers (hemoglobin with the iron in the ferric state)
(2) Hemepexin - binds free heme
(3) Transferrin - binds free iron
In heme degradation: globin is ___ to free amino acids; released iron is ___
hydrolyzed; recycled
Fill in the product and enzyme that catalyzes the reaction below, and reaction location:
Product: Biliverdin
Enzyme: Heme oxygenase
Location: spleen, endoplasmic reticulum
Fill in the product and enzyme that catalyzes the reaction below, and reaction location:
Biliverdin … (hint: reduction)
Product: Bilirubin
Enzyme: Biliverdin reductase
Location: spleen
Fill in the product and enzyme that catalyzes the reaction below, and reaction location:
Bilirubin … (hint: conjugation)
Product: Bilirubin Diglucuronide (conjugated)
Enzyme: Glucuronyl bilirubin transferase
Location: Liver, endoplasmic reticulum
Is bilirubin water soluble?
NO
*it is made water soluble by attachment of two sugar groups to the propionate side chains
Crigler-Najjar syndrome
Due to a deficiency in UDP-glucuronyl transferase and results in severe jaundice
Neonatal jaundice
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
What is the fate of conjugated bilirubin?
Liver –> bile canaliculi –> gall bladder –> intestinal tract
*Intestinal bacteria convert conjugated bilirubin to a series of urobilinogens and related products
Urobilinogen
colorless
Oxidation leads to the formation of urobilin, which contributes to the color of normal urine and feces
Jaundice
abnormalities in bilirubin metabolism
Prehepatic jaundice
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
Hepatic jaundice
Diseased condition of the liver (e.g. hepatitis, cirrhosis) that prevents uptake or conjugation of bilirubin
Posthepatic jaundice
Blockage of bile flow out of the liver and into the intestinal tract, build-up of conjugated bilirubin
Bilirubin is considered a major ___ in the blood for scavenging free radicals
anti-oxidant
What happens to iron during heme degradation?
It is stored in ferritin and hemosiderin (degraded form of ferritin)
An increase in iron entering tissues results in an ___ in ferritin content
increase
What does transferrin do for iron?
It transports it from the spleen (where RBCs are degraded) back to the marrow (where RBCs are synthesized)
Ferro-transferrin binds a receptor on the cell membrane at pH ___
7
Ferro- transferrin and its receptor are taken up by ___ in clathrin coated pits
endocytosis
The pH in the vesicle carrying ferro- transferrin and its receptor is lowered to pH ___ causing the dissociation of iron from transferrin
5
Receptor and apotransferrin are returned to the plasma membrane where the pH is ___ and the
transferrin will no longer bind its receptor
7
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
A. pancreatic cancer.
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.
A. Posthepatic jaundice.
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.
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.
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.
E. it can be caused by kidney failure.
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.
C. is made by the liver.
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.
A. to make it more water soluble.
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.
A. can lead to a build up of conjugated bilirubin in the body.
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.
C. carbon monoxide is produced.
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.
E. Crigler-Najjar syndrome.
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.
E. All of the above.
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.
E. undergoes receptor mediated endocytosis.
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.
D. Transferrin binds iron at low and neutral pH but not high pH.
