chmi 2227 - e.r. gauthier, ph.d. 1 chmi 2227e biochemistry i enzymes: - inhibition
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CHMI 2227 - E.R. Gauthier, Ph.D. 1
CHMI 2227EBiochemistry I
Enzymes:- Inhibition
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Enzyme inhibition
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Enzyme inhibitionExample 1 - VEGF Receptor inhibitors:
British Journal of Cancer (2005) 92(Suppl 1), S6 – S1Endothelial cell
VEGF
VEGF-R
Endothelial cell growth/migration
ZD6474
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Enzyme inhibitionExample 2 – Sildenafil:
Int.
J. Im
pot.
Res
. (20
04)
16, S
11–S
14
Endothelial cell Vascular smoothmuscle cell
Acetylcholine
Nit
ric
Ox
ide
S
yn
tha
se
(N
OS
)
NO
Arginine
NO Guanylate cyclase
GTP
cGMP
GMPMusclerelaxation Blood vessel
Dilation
PDE
Sildenafil
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Enzyme inhibitionExample 3 – Acetaminophen (tylenol):
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Trypsin inhibitor
Reversible Enzyme inhibition1- Competitive inhibition
P
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Reversible Enzyme inhibition1- Competitive inhibition
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Reversible Enzyme inhibition2- Uncompetitive inhibition
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Reversible Enzyme inhibition2- Uncompetitive inhibition
Vmaxapp= Vmax / (1 + [I]/Ki)
Kmapp= Km / (1 + [I]/Ki)
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Reversible Enzyme inhibition3- Noncompetitive inhibition
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Reversible Enzyme inhibition3- Noncompetitive inhibition
Vmaxapp= Vmax / (1 + [I]/Ki)
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Irreversible enzyme inhibition
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Irreversible enzyme inhibition1. Group-specific inhibitors
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Irreversible enzyme inhibition2. Affinity labels
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Irreversible enzyme inhibition3. Suicide inhibitors
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Irreversible enzyme inhibition3. Suicide inhibitors - penicillin
Structure of the bacterial cell wall
SugarsTetrapeptide
pentaGly bridges
Pen
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Irreversible enzyme inhibition3. Suicide inhibitors - penicillin
Tetrapeptide
pentaGly bridge
Glycopeptide transpeptidase
Glycopeptide transpeptidase
Glycopeptide transpeptidase
Penicillin
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Irreversible enzyme inhibition3. Suicide inhibitors - penicillin