-
enzyme catalyst MOA
reduce activation energy required, increasing rate of reaction
-
constant & theoretical maximal rate of the reaction
Vmax
-
-
-
under true M-M conditions, it is an estimate of the dissociation constant of E from S
Km
-
inhibitors that interact w/ an enzyme via noncovalent associations
reversible inhibitors
-
inhibitors that interact w/ an enzyme via covalent associations
irreversible inhibitors
-
2 types of reversible inhibitors
- competitive
- noncompetitive
-
inhibitor that binds only to E (NOT to ES)
competitive
-
inhibitor that binds either to E and/or to ES
noncompetitive
-
inhibitor that results in same Vmax, increased Km
competitive inhibitor
-
inhibitor that results in same Km, decreased Vmax
noncompetitive
-
inhibitors that bind reversibly to the active site
competitive
-
inhibitors that bind to other parts of the enzyme, distorting its shape & active site
noncompetitive
-
noncompetitive inhibitor ____ (can/cannot) be overcome by increasing [S].
cannot
-
competitive inhibitor _____ (can/cannot) be overcome by increasing [S]
can
-
difference between mixed inhibition & noncompetitive
EIS (enzyme inhibitor substrate) complex has residual enzymatic activity in mixed inhibition
-
inhibition that results in reduced Vmax and inc OR dec Km
mixed inhibition
-
inhibition where inhibitor binds only to the enzyme substrate complex
incompetitive
-
inhibition resulting in decreased Vmax AND Km by the same amount
uncompetitive
-
example of irreversibly enzyme inhibitor
serine protease inhibitors
-
serine protease that is a potent inhibitor of bacterial  -lactamase
clavulanic acid
-
principle enzyme responsible for penicillin-resistant bacteria
clavulanic acid
-
MOA of Michael acceptor against -lactamase
alkylates nucleophilic residue on -lactamase, causing irreversible inhibition
-
natural agonist of muscarinic-R's
muscarine
-
natural antagonist of muscarinic-R's
atropine
-
reversible AChE inhibitor from the African Calabar Bean
physostigmine
-
what is physostigmine used to treat?
- myasthenia gravis
- glaucoma
- Alzheimer's disease
- delayed gastric emptying
-
site on AChE alkylated by Sarin
esteratic site
-
how did pyridostigmine cause the Gulf War Syndrome?
under high stress (eg: at war), the BBB becomes leaky => pyridostigmine was able to get into the CNS & cause SE's
-
targeted anticancer drugs
tyrosine kinase inhibitors
-
Philadelphia Chromosome in CML
BCR-ABL fusion protein
-
4 steps for dev of imatinib
- 1) pyrimidine ring added to activate
- 2) amide for activity against BCR-ABL
- 3) methyl group to eliminate PKC activity
- 4) R1 changed to ring to inc water solubility/bioavailability
-
binds to inactive ABL
imatinib
-
binds to active ABL
dasatinib
-
molecular target of clavulanic acid
-lactamase
-
molecular target of neostigmine
reversible inhibitor of AChE
-
molecular target of nerve gas agents (Sarin, Tabun, DFP, VX)
irreversible AChE inhibitors
-
muscarine treats
glaucoma
-
atropine treats
organophosphate poisoning & resuscitation
-
neostigmine treats
myasthenia gravis (autoimmune)
-
molecular target of pralidoxime
removes irreversible organophosphate inhibitors from AChE
-
molecular target of pyridostigmine
prophylatic to block/prevent organophosphate binding to AChE
-
molecular target of imatinib (Gleevec)
competitive BCR-ABL inhibitor binds to inactive ABL
-
molecular target of dasatinib (Sprycel)
binds to active form of ABL
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