Erythrocyte Biochemistry

Question 1

Which of the following subunits make up fetal hemoglobin?

A. alpha2-beta2

B. alpha2-gamma2

C. gamma2-beta2

D. alpha2-alpha2

Answer 1

alpha2-gamma2

Question 2

Which of the following correctly describes the conformation change of Hb upon O2 binfing to the heme iron?

A. Hb decreases affinity for O2

B. The proximal histidine and distal histidine both pull down the globin chain

C. The distal histidine helps stabilze the O2

D. The proximal histidine moves up and and releases its interaction with the globin chain

Answer 2

The distal histidine helps stabilze the O2

Question 3

Which of the following correctly describes the effect of pH on O2 binding affinity of Hb?

A. Hb increases affinity for O2

B. Left Shift seen on O2 dissociation curve

C. Hb decreases affinity for O2

D. None of the above

Answer 3

Hb decreases affinity for O2

This is also seen in: increase 2,3-BPG, exercise or sickle cell anemia

Question 4

Why does HbF binds O2 better than HbA?

Answer 4

HbF does not bind 2,3-BPG well

Question 5

A third of our iron is stored in what 3 locations of our body?

Answer 5

Liver

Spleen

Bone Marrow

Question 6

Which of the following is able to bind Ferric Iron (Fe3)?

A. Hepcidin

B. Ferroportin

C. Feroxidase

D. Ferritin

Answer 6

Ferritin

Question 7

______ exports ferrous iron (Fe2) out of the cells and requires _________ to function. The exporting protein however is destroyed/regulated by ________

Answer 7

Ferroportin exports ferrous iron (Fe2) out of the cells and requires Hephaestin to function. The exporting protein however is destroyed/regulated by Hepcidin

Question 8

Which of the following is correct about the transport of iron in the blood?

A. Transferrin binds and transports Fe2

B. Transferrin binds and transports Ferrous

C. Hepcidin binds and transports ferric

D. Transferrin binds and transports Fe3

Answer 8

Transferrin binds and transports Fe3

Question 9

Which of the following is responsible for oxidizing animal product derived Ferrous to Ferric to be stored in Ferritin?

A. DMT-1 (Divalent Transporter)

B. Feroxidase/Cerruloplasmin

C. Feric Reductase

D. Duodenal Cytochrome-like B protein

E. C and D

F. A and B

Answer 9

Ferroxidase aka Cerruloplasmin

Question 10

Which of the following is responsible for reducing Ferric to Ferrous in the presence of Vitamin C?

A. DMT-1 (Divalent Transporter)

B. Feroxidase/Cerruloplasmin

C. Feric Reductase

D. Duodenal Cytochrome-like B protein

E. C and D

F. A and B

Answer 10

C and D

Ferric Reductase

Duodenal Cytochrome-like B protein (dcytb)

Question 11

Which of the following correctly expresses how transferrin is removed?

A. Combustion via an oxidation reaction

B. REceptor mediated endocytosis and internalized via COP2 coated puts into endosomes

C. TfR enodocytoses transferrin into clathrin coated pits

D. None of the above

Answer 11

TfR enodocytoses transferrin into clathrin coated pits

Question 12

Which of the following regulates the expression of Hepcidin in the liver?

A. Human Homeostatic Iron Regulator Protein that is initiated irrespective of iron levels

B. HFE that is responsive to iron levels

C. Presence of Hemosiderin

D. None of the above

Answer 12

HFE that is responsive to iron levels

Question 13

When iron levels are low which of the following is most likely to be occuring?

A. Hepcidin expression: decreases, Ferroportin: increases, Iron Absorption: increases

B. Hepcidin expression: increases , Ferroportin: decreases , Iron Absorption: decreases

C. Hepcidin expression: decreases , Ferroportin: increases , Iron Absorption: decreases

D. Hepcidin expression: decreases , Ferroportin: decreases , Iron Absorption: decreases

Answer 13

A. Hepcidin expression: decreases, Ferroportin: increases, Iron Absorption: increases

Question 14

Which of the following is the correct clinical presentation of Hereditary Hemochromatosis?

A. IRon absorption decreases in heart, liver, and pancreas begin to fail

B. Iron absorption increases and accumulates in the bone marrow, heart, and spleen

C. Iron absorption increases and accumulates in the heart, liver, and pancreas

D. None of the above

Answer 14

Iron absorption increases and accumulates in the heart, liver, and pancreas

NOTE: HH is iron overload

Question 15

RBC production is dependent on what two substances, who’s absence would lead to Megaloblastic anemia?

Answer 15

Folate (folic acid)

B12 (cobalamin)

Question 16

Which of the following is the active form of folate, which is important for DNA synthesis due to its involvement with synthesis of purines and pyrimidine thymine?

A. THF

B. DHF

C. BHF

D. All of the above are considered active forms

Answer 16

THF

Question 17

What is the effect of methotrexate in folate synthesis?

A. Failure to absorb Folic Acid in the small intestines (jejunum)

B. Irradication fo Bqw

C. Inhibition of DHF reductase leading

D. None of the above

Answer 17

Inhibition of DHF reductase leading

Question 18

A deficiency in vitamin B12 can result from lack of intrinsic factor. BEcause of this we can develop a folate trap where we would most liekly see the buildup of which of the following?

A. FH4

B. DHB

C. N5-methyl THF

D. All of the above

Answer 18

N5-methyl THF

FH4 is what we wouldn’t be able to make, or at least would have very low levels of

Question 19

Which of the following substances is made in the stomach and carries B12 to the ileum where it’s released into the blood stream?

A. R-binding protein

B. Intrinsic Factor

C. Transcobalamine II

D. Methotrexate

Answer 19

Intrinsic Factor

Question 20

Which of the following substances carries B12 complex until its taken up into the cells?

A. R-binding protein

B. Intrinsic Factor

C. Transcobalamine II

D. Methotrexate

Answer 20

Transcobalamine II

Question 21

T/F: When performing a Schilling Test, if radiolabeled B12 is not present in the urine then we test again with intrinsic factor present

Answer 21

True

Question 22

Heme Biosynthesis happens primarily in the liver and erythroid cells of the bone marrow. It occurs in three steps. Name those 3 steps and the enzymes involved

Answer 22

1. Generation of ALA w/ ALA synthase
2. Generation of Coproporphyrinogen III w/ PBG deaminase
3. Generation of Protoporphyrin and introduction of iron

w/ Protoporphyrinogen Oxidase

(All Cop Prototype APP)

Question 23

ALA synthase involved in forming ALA from succinyl coA and glycine requires which of the following substrates or RBCs will present as pale?

A. B12

B. Niacin

C. Vitamin C

D. B6 (pyridocal phosphate)

Answer 23

B6 (pyridocal phosphate)

Question 24

Lead poisoning lowers heme production by inactivating which of the following enzymes?

A. Protophyrinogen Oxidase and ALA dehydrogenase

B. PBG deaminase and Ferrochelatase

C. ALA dehydrogenase and Ferrochelatase

D. PBG demanisae and PRotophyrinogen Oxidase

Answer 24

ALA dehydrogenase and Ferrochelatase

NOTE: this causes build up of both ALA and protoporphyrin IX, and ALA is neurotoxic

Question 25

Which of the following poryphrias is caused by PBG demaniase mutation, and results in symptoms of abdominal pain and neurological dysfunction? A. Acute Intermittent Poryphyria B. Congenital Erythropoietic Porphyria C. Porphyria Cutanea Tarda D. Variegate Porphyria

Answer 25

Acute Intermittent Poryphyria

Question 26

Which of the following poryphrias is caused by Uroporphyrinogen III synthase is effected in erythrocytes, and results in photosensitivity and red colored urine and teeth? A. Acute Intermittent Poryphyria B. Congenital Erythropoietic Porphyria C. Porphyria Cutanea Tarda D. Variegate Porphyria

Answer 26

Congenital Erythopoietic Poyphyria

Question 27

Which of the following poryphrias would you see an accumulation of uroporyphrinogen 3 leading to red wine colored urine, that’s caused by a defect in uropophyrinogen decarboxylase? A. Acute Intermittent Poryphyria B. Congenital Erythropoietic Porphyria C. Porphyria Cutanea Tarda D. Variegate Porphyria

Answer 27

Porphyria Cutanea Tarda NOTE: it's the most common in the US

Question 28

Which of the following poryphrias is caused by a defect protoporphrinogen IX oxidase? What is another name for this porphyrias? A. Acute Intermittent Poryphyria B. Congenital Erythropoietic Porphyria C. Porphyria Cutanea Tarda D. Variegate Porphyria

Answer 28

Variegate Porphyria Celebrity Poryphyria

Question 29

The heme degredation is handled by reticulo-endothelial system, that degrades hemoglobin into globin (becomes AA) and heme (processed for degredation).

Answer 29

Cool

Question 30

Which of the following enzymes can remove the bridge between the pyrrole rings of heme? A. Biliverdin Reductase B. Heme Oxygenase C. Heme oxygenase with O2 B. UDP-glucoronyl transferase

Answer 30

Heme oxygenase with O2

Question 31

Which of the following enzymes reduces biliverdin to bilirubin? A. Biliverdin Reductase B. Bilirubin Synthase C. Heme oxygenase with O2 B. UDP-glucoronyl transferase

Answer 31

Biliverdin Reductase

Question 32

Free/unconjugated/indirect bilirubin is insoluble and converted to its conjugated form in which of the following scenarios? A. Liver UDP-glucoronyl transferase B. Spleen UDP-glucoronyl reductase C. Liver UDP-glucoronyl reducatase D. None of the above

Answer 32

Liver UDP-glucoronyl transferase

Question 33

Correclty label the type of jaundice that is described below: 1. Increased production of unconjugated BR 2. Impaired hepatic uptake, conjugation, or secretion of conjugated BR as seen in Criggler Najjar syndrome and Gilbert Syndrome 3. Problems with bilirubin secretion where we see dark urine

Answer 33

1. **Prehepatic Jaundice:** Increased production of unconjugated BR 2. **Intrahepatic Jaundice:** Impaired hepatic uptake, conjugation, or secretion of conjugated BR as seen in Criggler Najjar syndrome and Gilbert Syndrome 3. **Post-hepatic Jaundice**Problems with bilirubin secretion where we see dark urine

Question 34

What is the difference between Cirggler Najjar Syndrome I vs II in neonatal jaundice

Answer 34

Type I the UDP-GT enzyme is absent, while in Type II the UDP-GT enzyme is impaired and less active

Question 35

T/F: in hepatitis you see elevated levels of unconjugated and conjugated BR in the blood , with a dark tea colored urine

Answer 35

True