Midterm 2 Open Answers

Question 1

What kind of covalent bond is formed between thrombin and antithrombin?

Answer 1

ester bond between active Ser and the carboxylic group of the cleaved peptide bond in antithrombin

Question 2

Which is the cofactor in the thrombin catalyzed activation of F XIII ?

Answer 2

fibrin

Question 3

Write down the substrates and products of the reaction catalyzed by FXIIIa (Name the amino acids in the substrates and the name of the formed bond)

Answer 3

S: lysine and glutamine side chains in gamma and alpha chains of fibrinP: gamma-glutamyl-lysine isopeptide and ammonia

Question 4

What kind of covalent bond is formed between thrombin and α2-macroglobulin?

Answer 4

isopeptide bond between an ε–amino group of Lys in thrombin and a carboxylic group from a Gln-Cys thioester bond in α2-macroglobulin

Question 5

Which proteases are necessary for the destruction of the intrinsic tenase and the prothrombinase complexes ?

Answer 5

thrombin, activated protein C

Question 6

Which protein cofactors are necessary for the destruction of the intrinsic tenase and the prothrombinase complexes?

Answer 6

thrombomodulin, protein S

Question 7

What is the mode of action of streptokinase ?

Answer 7

forms a complex with human plasminogen, in which plasminogen gains activity as plasminogen activator

Question 8

List two distinct functions of von Willebrand factor

Answer 8

carrier of F VIII, mediator of platelet adhesion at high shear

Question 9

What is the mode of antithrombolytic action of TAFI (Thrombin activatable fibrinolysis inhibitor)?

Answer 9

cleaves C-terminal Lys residues and decreases the binding sites for tPA and plasminogen in fibrin and moderates the cofactor of fibrin in plasminogen activation

Question 10

What kinds of conjugation occur in 2nd phase of biotransformation ?

Answer 10

glucuronidation, sulfation, glutatione conjugation, acetylation, amino acid conjugation, methylation

Question 11

Which enzymes catalyze glucuronidation ?

Answer 11

UDP-glucuronosyl-transferases

Question 12

Name diseases caused by gene expression disorders of UDP-glucuronosyl-transferases!What kind of hyperbilirubinemia is caused by them ?

Answer 12

Gilbert disease, Criegner-Najjar syndromeunconjugted bilirubin

Question 13

What is the dominant type of conjugation in case of electrophilic intermediates?

Answer 13

glutathione conjugation

Question 14

What are the steps of glutathione conjugation?

Answer 14

conjugation with glutatione, loss of glutamate and glycine, conjugation with acetyl group

Question 15

Which pathways of the intermediary metabolism involve biotransformation reactions?

Answer 15

cholesterol synthesis, steroid biosynthesis, bile acid synthesis, bile acid conjugation, eicosanoid synthesis-conjugation, leukotriene formation, bilirubin conjugation, catecholamine synthesis

Question 16

What is the role of the primary cilium of endothelial cells?

Answer 16

Detect flow rate and cause intracellular change in calcium concentration

Question 17

Which compound forms a secondary matrix in thrombi in addition to thrombin?

Answer 17

NETs: Neutrophil Extracellular Traps

Question 18

Write down the targets of TFPI in the order of their binding

Answer 18

Forms complex with Xa and inhibits it, then goes on to bind and inhibit VIIa

Question 19

Which phase of biotransformation is mediated by transporters?

Answer 19

Phase III

Question 20

What is the dominant chemical reaction in the 1st phase of biotransformation?

Answer 20

Hydroxylation

Question 21

What enzymes catalyze the majority of the reactions in the 1st phase of biotransformation?

Answer 21

Cytochrome P450 monooxygenase complex family

Question 22

What kind of solubility change is caused by biotransformation reactions?

Answer 22

Substance is made more water-soluble so that it can be excreted

Question 23

What is the first enzyme component of the microsomal respiratory chain and what is the electron donor?

Answer 23

Enzyme: Cytochrome P450 ReductaseDonor: NADPH

Question 24

List 3 major targets of thrombin in the positive-feedback loops in blood plasma

Answer 24

Factors V, VIII, and XI

Question 25

List at least 3 different in vivo triggers of the intrinsic pathway of blood coagulation (through activation of factor XII)

Answer 25

NET, polyphosphates, RNA

Question 26

What are the sources of polyphosphates in vivo?

Answer 26

Platelets

Question 27

Name some organs which express P450 isoenzymes involved in drug metabolism

Answer 27

Liver, skin, intestines, lungs

Question 28

What is the electron donor for monooxygenases in drug metabolism?

Answer 28

NADPH

Question 29

What kind of ROS can be formed during P450 monooxygenation?

Answer 29

Superoxide Anion

Question 30

What are the phases of biotransformation?

Answer 30

Phase I: PreparationPhase II: ConjugationPhase III: Excretion

Question 31

Which phases of biotransformation are mediated by enzymes?

Answer 31

Phase I (CYP450 monooxygenases)Phase II (UGT, ST, GST, AT, MT, Acetyltransferases)

Question 32

What is the cofactor for glucuronidation?

Answer 32

UDP-Glucuronate