Midterm 2 Open Answers Flashcards
What kind of covalent bond is formed between thrombin and antithrombin?
ester bond between active Ser and the carboxylic group of the cleaved peptide bond in antithrombin
Which is the cofactor in the thrombin catalyzed activation of F XIII ?
fibrin
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)
S: lysine and glutamine side chains in gamma and alpha chains of fibrinP: gamma-glutamyl-lysine isopeptide and ammonia
What kind of covalent bond is formed between thrombin and α2-macroglobulin?
isopeptide bond between an ε–amino group of Lys in thrombin and a carboxylic group from a Gln-Cys thioester bond in α2-macroglobulin
Which proteases are necessary for the destruction of the intrinsic tenase and the prothrombinase complexes ?
thrombin, activated protein C
Which protein cofactors are necessary for the destruction of the intrinsic tenase and the prothrombinase complexes?
thrombomodulin, protein S
What is the mode of action of streptokinase ?
forms a complex with human plasminogen, in which plasminogen gains activity as plasminogen activator
List two distinct functions of von Willebrand factor
carrier of F VIII, mediator of platelet adhesion at high shear
What is the mode of antithrombolytic action of TAFI (Thrombin activatable fibrinolysis inhibitor)?
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
What kinds of conjugation occur in 2nd phase of biotransformation ?
glucuronidation, sulfation, glutatione conjugation, acetylation, amino acid conjugation, methylation
Which enzymes catalyze glucuronidation ?
UDP-glucuronosyl-transferases
Name diseases caused by gene expression disorders of UDP-glucuronosyl-transferases!What kind of hyperbilirubinemia is caused by them ?
Gilbert disease, Criegner-Najjar syndromeunconjugted bilirubin
What is the dominant type of conjugation in case of electrophilic intermediates?
glutathione conjugation
What are the steps of glutathione conjugation?
conjugation with glutatione, loss of glutamate and glycine, conjugation with acetyl group
Which pathways of the intermediary metabolism involve biotransformation reactions?
cholesterol synthesis, steroid biosynthesis, bile acid synthesis, bile acid conjugation, eicosanoid synthesis-conjugation, leukotriene formation, bilirubin conjugation, catecholamine synthesis
What is the role of the primary cilium of endothelial cells?
Detect flow rate and cause intracellular change in calcium concentration
Which compound forms a secondary matrix in thrombi in addition to thrombin?
NETs: Neutrophil Extracellular Traps
Write down the targets of TFPI in the order of their binding
Forms complex with Xa and inhibits it, then goes on to bind and inhibit VIIa
Which phase of biotransformation is mediated by transporters?
Phase III
What is the dominant chemical reaction in the 1st phase of biotransformation?
Hydroxylation
What enzymes catalyze the majority of the reactions in the 1st phase of biotransformation?
Cytochrome P450 monooxygenase complex family
What kind of solubility change is caused by biotransformation reactions?
Substance is made more water-soluble so that it can be excreted
What is the first enzyme component of the microsomal respiratory chain and what is the electron donor?
Enzyme: Cytochrome P450 ReductaseDonor: NADPH
List 3 major targets of thrombin in the positive-feedback loops in blood plasma
Factors V, VIII, and XI
List at least 3 different in vivo triggers of the intrinsic pathway of blood coagulation (through activation of factor XII)
NET, polyphosphates, RNA
What are the sources of polyphosphates in vivo?
Platelets
Name some organs which express P450 isoenzymes involved in drug metabolism
Liver, skin, intestines, lungs
What is the electron donor for monooxygenases in drug metabolism?
NADPH
What kind of ROS can be formed during P450 monooxygenation?
Superoxide Anion
What are the phases of biotransformation?
Phase I: PreparationPhase II: ConjugationPhase III: Excretion
Which phases of biotransformation are mediated by enzymes?
Phase I (CYP450 monooxygenases)Phase II (UGT, ST, GST, AT, MT, Acetyltransferases)
What is the cofactor for glucuronidation?
UDP-Glucuronate
