This set of Protein Engineering Multiple Choice Questions & Answers (MCQs) focuses on “Applications – Engineering Blood Clotting Factor VIII – 1”.
1. Which of the following is not likely to play a role in clotting of blood?
a) Fibrinogen
b) Platelets
c) Clotting factors
d) Antibodies
View Answer
Explanation: Antibodies are not likely to play a role in clotting of blood. Fibrinogen, platelets, and clotting factors are likely to play a role in clotting of blood. The blood has a finely tuned mechanism for forming clots, but only when needed.
2. Which of the following clotting factor is deficient in people suffering from haemophilia A?
a) Factor V
b) Factor VI
c) Factor IX
d) Factor VIII
View Answer
Explanation: Factor VIII is the clotting factor that is deficient in people suffering from haemophilia A. Factor V, Factor VI, and Factor IX are not deficient in people suffering from haemophilia A. Haemophilia is a genetic disease, carried by females but only affecting their sons. Queen Victoria was a famous carrier.
3. In majority of the cases haemophilia A is inherited as an X-linked recessive trait.
a) False
b) True
View Answer
Explanation: The above statement is true. In majority of the cases haemophilia A is inherited as an X-linked recessive trait, though there are cases which arise from spontaneous mutations. It is a genetic deficiency in clotting factor VIII, which causes increased bleeding and usually affects males.
4. Which of the following is a bypassing agent, that circumvents the inhibitor to provide hemostasis?
a) Recombinant factor X (FX)
b) Recombinant factor IX (FIX)
c) Recombinant activated factor VIII (FVIIIa)
d) Recombinant activated factor VII (FVIIa)
View Answer
Explanation: Recombinant activated factor VII (FVIIa) is a bypassing agent, that circumvents the inhibitor to provide hemostasis. Recombinant factor X (FX), recombinant factor IX (FIX), and recombinant activated factor VIII (FVIIIa) are not bypassing agents. Activated prothrombin complex concentrate (aPCC) is also a bypassing agent.
5. Most early gene therapy studies were focused on haemophilia B, despite the fact that haemophilia B accounts for only 20 % of all haemophilia cases.
a) False
b) True
View Answer
Explanation: The above statement is true. Most early gene therapy studies were focused on haemophilia B, despite the fact that haemophilia B accounts for only 20 % of all haemophilia cases. Full length factor VIII cDNA (7 kb) exceeds the packaging capacity of AAV vectors (∼4.7 kb). The full length of factor IX cDNA is ∼1.6 kb.
6. Which of the following is the first non-factor prophylactic bypassing agent that was recently approved for haemophilia A patients with and without inhibitors?
a) Tocilizumab
b) Itolizumab
c) Hemilizumab
d) Emicizumab
View Answer
Explanation: Emicizumab is the first non-factor prophylactic bypassing agent that was recently approved for haemophilia A patients with and without inhibitors. Emicizumab (hemlibra) is a bispecific antibody that acts as a FVIIIa – mimetic with procoagulant activity.
7. Which of the following mostly activates FVIII during coagulation?
a) Plasmin
b) Furin
c) Fibrin
d) Thrombin
View Answer
Explanation: FVIII is mostly activated by thrombin during coagulation. Once activated (FVIIIa) it acts as a co-factor for activated FIX (FIXa), which is responsible for the activation of factor X (FX). Plasmin, furin, or fibrin do not activate FVIII during coagulation.
8. What is the molecular weight of full length FVIII protein?
a) 170 kDa
b) 210 kDa
c) 310 kDa
d) 280 kDa
View Answer
Explanation: The molecular weight of full length FVIII protein is 280 kDa. Full length FVIII is a large, 280 kDa protein primarily expressed in liver sinusoidal endothelial cells (LSECs), as well as extra-hepatic endothelial cells.
9. Factor VIII predominantly circulates as a homodimer.
a) True
b) False
View Answer
Explanation: The above statement is false. Factor VIII predominantly circulates as a heterodimer of the heavy chain and the light chain bound through non-covalent metal dependent interactions. The heavy chain is composed of the A1-, A2-, and B-domain. The light chain is composed of the A3-, C1-, and C2- domain.
10. Which of the following clotting factor is deficient in people suffering from haemophilia B?
a) Factor V
b) Factor VII
c) Factor VIII
d) Factor IX
View Answer
Explanation: Factor IX is the clotting factor that is deficient in people suffering from haemophilia B. Factor V, Factor VII, or Factor VIII are not deficient in people suffering from haemophilia B. Haemophilia B is an X-linked bleeding disorder due to inheritable deficiencies in clotting factor IX.
11. Which of the following domain is the cleavage site for furin enzyme?
a) A domain
b) A2 domain
c) C1 domain
d) B domain
View Answer
Explanation: B domain is the cleavage site for furin enzyme. A domain, A2 domain, or C1 domain are not cleavage sites for furin enzyme. The formation of heterodimer is due to the proteolytic cleavage by the intracellular proprotein convertase furin within the B domain at either R-1313 and/or R-1648.
12. The FVIII heavy chain and light chain dissociate after cleavage by the furin.
a) True
b) False
View Answer
Explanation: The above statement is false. The FVIII heavy chain and light chain do not dissociate after cleavage by the furin The FVIII heavy chain (A1-a1-A2-a2-B) and light chain (a3-A3-C1-C2) remain associated through non-covalent metal-ion-dependent interactions occurring between the A1 and A3 domains.
13. Which of the following is responsible for the activation of factor X (FX) during sustained coagulation?
a) Activated Factor V (FVa)
b) Activated Factor VIII (FVIIIa)
c) Activated Factor XII (FXIIa)
d) Activated Factor IX (FIXa)
View Answer
Explanation: Activated Factor IX (FIXa) is responsible for the activation of factor X (FX) during sustained coagulation. During coagulation, FVIII is activated mostly by thrombin. Once activated (FVIIIa), it acts as a cofactor for the activated FIX (FIXa). Activated Factor V (FVa), activated Factor VIII (FVIIIa), or activated Factor XII (FXIIa) are not responsible for the activation of factor X (FX) during sustained coagulation.
14. Where in the cell does the cleavage of B domain (of FVIII) occurs by protease furin?
a) Endoplasmic Reticulum
b) Mitochondria
c) cis region of golgi apparatus
d) trans region of golgi apparatus
View Answer
Explanation: The cleavage of B domain (of FVIII) occurs by protease furin in the trans region of golgi apparatus. It does not occur in the endoplasmic reticulum, mitochondria, or cis region of golgi apparatus. Proteolytic cleavage of FVIII at R-1313 and/or R-1648 by the trans-golgi protease furin results in heterodimer formation.
15. Which of the following factor is also known as an anti-hemophilic factor?
a) Factor VII
b) Factor V
c) Factor VI
d) Factor VIII
View Answer
Explanation: Bloodclotting factor VIII (FVIII) is known as an anti-hemophilic factor. Factor VII, factor V, and factor VI are not known as an anti-hemophilic factor. The blood clotting factor is the nonenzymatic cofactor to the activated clotting factor IX (FIXa). When this is proteolytically activated it interacts with FIXa to form a tight non-covalent complex. This binds to and activates factor X (FX). FVIII gene defects may cause hemophilia A.
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