Term
| what 2 chemicals are released from platelets when they become activated? |
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Definition
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Term
| What do NSAIDS like aspirin and ibuprofen inhibit? |
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Definition
| COX>>>TXA2>>>platelet aggregation |
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Term
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Definition
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Term
| what does phosphatase do? |
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Definition
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Term
| what does glycogen phosphorylase do? |
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Definition
| breaks glycogen down into glucose |
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Term
| what does glycogen synthase do? |
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Definition
| makes glycogen from glucose |
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Term
| what makes glycogen phosphorylase more active? |
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Definition
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Term
| what makes glycogen synthase less active? |
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Definition
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Term
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Definition
| cuts peptide bonds and causes activation |
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Term
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Definition
takes glucose and ATP>>>glucose-P and ADP
can be active at very low levels of glucose |
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Term
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Definition
| different proteins that catalyze the same reaction |
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Term
| what does glucokinase do? |
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Definition
enzyme in liver that makes glycogen from glucose
works only when there are high levels of glucose (after a meal) |
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Term
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Definition
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Term
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Definition
| hydrolyzes a peptide bond in chymotrypsinogen and activates it to chymotrypsin |
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Term
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Definition
| gets rid of dangerous peroxide |
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Term
| what are hydrolases and give an example |
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Definition
| enzymes that break bonds by adding water; phosphatase (removes a phosphate) |
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Term
| how does a transition state analog inhibit an enzyme? |
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Definition
| they bind tightly to the active site and prevent substrate binding |
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Term
| what is a noncompetitive inhibitor? |
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Definition
| the inhibitor binds somewhere other than the active site; the substrate can still bind to the active site, but it will not form a product |
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Term
| what kind of inhibitor is aspirin? |
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Definition
| irreversible inhibitor bc it chemically changes the active site on COX |
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Term
| what kind of inhibitor is ibuprofen? |
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Definition
| reversible inhibitor (competitive)-just sits in the active site |
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Term
| what are organophosphorous compounds? |
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Definition
| irreversibly inhibit acetylcholinesterase (and other serine-active sites) |
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Term
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Definition
| binds to acetylcholine receptors (without activating them) and then new acetylcholine esterase can be regenerated |
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Term
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Definition
removes organophosphate from the acetylcholinesterase
reactivates the esterase |
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Term
| what is the fastest possible means of enzyme regulation? |
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Definition
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Term
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Definition
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Term
| What does thrombin do to fibrinogen? |
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Definition
| it cleaves off FpA and FpB-this removes negative charges-making fibrin insoluble and it aggregates and forms a clot |
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Term
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Definition
| stabilizes clot into hard clot (crosslinks) |
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Term
| what 2 amino residues are involved in the final crosslinking of a hard clot? |
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Definition
| lysine and glutamine side chains |
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Term
|
Definition
procoagulation (plug and clot formation)
anticoagulation (inhibition of clot)
fibrinolysis (dissolution of clot) |
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Term
| initiating event of platelet plug? |
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Definition
| exposure of subendothelium |
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Term
| 2 types of subendothelium adhesion molecules |
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Definition
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Term
|
Definition
1) adhesion
2) binds F8 for stability |
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Term
|
Definition
COX inhibitor
inhibits COX from changing arachidonic acid to thromboxane>>>platelet aggregation |
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Term
| why is fibrinogen highly negative? |
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Definition
| GLU, ASP, and sulfated TYR |
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Term
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Definition
| y-carboxyglu post-translational modifications |
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Term
| what is the required cofactor for the glu carboxylating reaction? |
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Definition
| reduced form of vitamin K: KH2 |
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Term
| name 3 vitamin K deficiency states |
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Definition
newborns (sterile gut)
prolonged antibiotics
problems with fat absorption (cystic fibrosis, gall stones) |
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Term
| what is the direct effect of carboxylation of the yc in glutamates of factors 2,7,9,10? |
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Definition
| stronger affinity for Ca++ |
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Term
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Definition
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Term
| what brings the prothrombin precursor to the surface of the platelet? |
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Definition
| Ca++ (held by negative charge on platelet membrane and gla residues on prothrombin) |
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Term
| why does prothrombin want to become bound to platelet surface? |
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Definition
| because F5a and F10a and also bound to platelet surface, and these factors active prothrombin into thrombin |
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Term
| what does warfarin and dicoumeral essentially do? |
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Definition
| inhibits Vit K reductases, which keep vit K in the KO form (which is inactive) |
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Term
| step by step mechanism of warfarin and coumeral |
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Definition
| inhibits vitamin K reductase>>>keeps Vit KO in oxidized form>>>inactive>>>slows Vit KH2-dependent carboxylase>>>slows GLA formation>>>prothrombin won't bind to platelet membrane>>>prothrombin won't become activated |
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Term
| where does carboxylation happen? |
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Definition
| in the liver (before the factors are released into blood) |
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Term
| how can Factors be regulated if they are irreversibly activated by proteolysis? |
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Definition
| they have short lifetimes |
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Term
| how are protein cofactors 5 and 8 degraded? |
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Definition
| by serum protease thrombin-activated protein C and protein S |
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Term
|
Definition
| serine protease inhibitor |
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Term
|
Definition
| suicide inactivator of thrombin; a major serpin |
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Term
| what do circulating heparins do? |
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Definition
| help AT3; enhance irreversible inhibition of thrombin |
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Term
| describe structure of heparin |
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Definition
| highly sulfated GAG: adds negative charge |
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Term
| what is a bad side effect of using heparin? |
|
Definition
HIT: heparin-induced thrombocytopenia
autoimmune response when antibodies are generated to a HMWH paltelet complex |
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Term
|
Definition
| activated platelets: excessive thrombi>>>multiorgan failure |
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Term
| what happens after damaged vessel has been repaired? |
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Definition
| fibrinolysis: serine protease plasmin cleaves fibrin clot into soluble peptide fragments |
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Term
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Definition
| tissue plasminogen activator |
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Term
| what post translational modification requires Vitamin K as a cofactor? |
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Definition
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|
Term
| which clotting factors contain y-carboxyglu (gla domains) |
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Definition
|
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Term
|
Definition
| reduction (via reductase) |
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Term
| 4 control mechanisms for anticoagulation |
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Definition
factor activation is localized
blood flow carries dilutes factors
Proteins C and S degrade cofactors 5 and 8
heparin enhances AT3 to degrade thrombin |
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Term
| what are the 5 A's of bleeding risks? |
|
Definition
Alcohol (where clotting factors are made)
Aspirin (blocks COX, no TXA2 is made>>>affects thrombosis)
Antibiotics (synthesis of vitamin K by bacteria-lowers GLA formation and slows rate of activation)
Anticancer drugs (slows bone marrow cells>>>platelet precursors)
Anticoagulant |
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Term
|
Definition
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Term
|
Definition
| deficiency of functional factor 8 |
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|
Term
| what does the PTT show for someone with Hemophilia A |
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Definition
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|
Term
| what does PT show for Hemophilia |
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Definition
|
|
Term
| what does platelet count and function test show for Hemophilia |
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Definition
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|
Term
| what does PTT show for Hemophilia Type B |
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Definition
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|
Term
| Etiology of von Willebrand's Disease |
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Definition
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|
Term
| what does platelet function test time do with vW's Disease and why |
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Definition
| lengthens-vWF is needed for platelets to adhere to vessel |
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|
Term
| deficiency of what factor may result from v W's Disease? |
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Definition
|
|
Term
| how does liver disease affect Clotting |
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Definition
| carboxylation of clotting factors (vitamin K dependent) occurs in the liver |
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|
Term
| how does coumadin affect vit k? |
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Definition
| inhibits Vit K reductase>>>stays in KO form=inactive |
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|
Term
| how long before surgery is aspirin stopped? |
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Definition
| 10 days (inhibits COX in platelets-platelets take 10 days to regenerate) |
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|
Term
| how long before surgery is coumadin stopped? |
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Definition
|
|
Term
| how long before surgery is heparin stopped? |
|
Definition
|
|
Term
| what does aspirin do to platelets? |
|
Definition
| inhibits COX in platelets>>>inhibits TXA2, which promote platelet aggregation |
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|
Term
| what are the Vitamin K dependent factors |
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Definition
|
|
Term
| what initiates the intrinsic pathway |
|
Definition
| factor 7 binding to the subendothelial collagen |
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|
Term
| function of reverse transcriptase? |
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Definition
| turns viral RNA to viral DNA |
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|
Term
| describe active site of HIV protease |
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Definition
| dimer of equivalent subunits: the active site has 2 aspartates at the interface |
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Term
| what role does aspartic acid residues in the active site of HIV protease serve? |
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Definition
|
|
Term
| basic structure of HIV protease inhibitor |
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Definition
| all have a hydroxy ethylene group (for tight binding to the active site) |
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|
Term
| why is an HIV protease an ideal target? |
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Definition
| because our bodies don't use them; we don't need them |
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Term
| what is the overall cell wall transpeptidase reaction in forming final stabilization crosslink in bacteria |
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Definition
| the terminal glycine (from the pentaglycine bridge) binds to the D-ala D-ala unit and one of the D-ala subunits are eliminated |
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|
Term
| 2 structural features of penicillin? |
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Definition
| beta lactam ring free carboxyl group with 2 methyl groups |
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|
Term
| what does penicillin do to transpeptidase? |
|
Definition
| inactivates it (irreversible suicide inhibitor) |
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|
Term
| what does clavulinic acid do? |
|
Definition
| suicide inactivator of beta lactamase |
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|
Term
| describe kinetics of competitive inhibition |
|
Definition
Vmax stays the same, bc if you get enough substrate in, its possible to reach vmax
KM increases bc it requires more substrate to reach the same level of activity (1/2 v max) |
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|
Term
| 3 enzymes involved when HIV replicates itself |
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Definition
Reverse transcriptase
Integrase
HIV protease |
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|
Term
| Go through steps how HIV retrovirus replicates itself |
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Definition
| Viral RNA (with Reverse transcriptase)>>>Viral DNA (with integrase)>>>integrates into Host DNA "Provirus">>>makes viral mRNA>>>forms Viral poly protein (with HIV protease)>>>cuts into individual viral proteins |
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|
Term
| what kind of protease is HIV protease |
|
Definition
| aspartyl protease (ASP active site, like pepsin) |
|
|
Term
| structure of HIV protease |
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Definition
| 2 identical subuntis that form a dimer with 2 ASP active sites at the interface |
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|
Term
| key structure in HIV protease inhibitor |
|
Definition
| hydroxy ethylene group (mimics tightly binding tetrahedral intermediate of substrate) |
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|
Term
| what does transpeptidase do? |
|
Definition
| catalyzes last step in cell wall biosynthesis-forms final crosslink in bacteria cell walls |
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|
Term
| how do bacteria die from penicillin? |
|
Definition
| bacterial cell wall becomes weakened; succumbs to osmotic stress, and explodes |
|
|
Term
| what is transpeptidase's active site? |
|
Definition
|
|
Term
| what does transpeptidases active site do? |
|
Definition
| attacks a carbonyl carbon in a D-ala---D-ala and forms an acyl-enzyme intermediate (the other D-ala is eliminated) |
|
|
Term
| 3 structural features of penicillin that makes it look like the normal substrate for transpeptidase |
|
Definition
beta lactam ring
2 methyl groups
free carboxyl |
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|
Term
| how does penicillin work on transpeptidase? |
|
Definition
| penicillin tricks transpeptidase into thinking that it is the normal substrate (D-ALA---D-ALA), so it forms an acyl-enzyme intermediate; chemistry is done on the enzyme, and the complex is inactivated>>>cell wall does not form final crosslink and the cell wall is weakened |
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|
Term
| what kind of inhibition is penicillin |
|
Definition
| irreversible suicide inactivator |
|
|
Term
| how do bacteria become resistant to penicillin |
|
Definition
| bacteria make beta-lactamase, which breaks the highly reactive beta lactam ring in penicillin by hydrolysis |
|
|
Term
|
Definition
| suicide inactivator of beta lacatmase |
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