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Competitive Inhibition
Product
C-OO-
Substrate
Competitive Inhibitor
Succinate
Glutarate
Malonate
C-OO-
C-OO-
C-OO-
C-H
H-C-H
H-C-H
C-H
H-C-H
H-C-H
C-OO-
C-OO-
H-C-H
Oxalate
C-OOC-OO-
C-OO-
H-C-H
C-OO-
Succinate Dehydrogenase
Adapted from Kleinsmith & Kish (1995) Principles of Cell and Molecular Biology (2e) p.49
Sulfa Drug Is Competitive Inhibitor
Domagk (1939)
Para-aminobenzoic acid (PABA)
H2N-
-COOH
Bacteria needs PABA for
the biosynthesis of folic acid
Folic
acid
Precursor
H2N-
-SONH2
Tetrahydrofolic acid
Sulfa drugs has similar
structure with PABA, and
inhibit bacteria growth.
Sulfanilamide
Sulfa drug (anti-inflammation)
Adapted from Bohinski (1987) Modern Concepts in Biochemistry (5e) p.197
Enzyme Inhibitors Are Extensively Used
● Sulfa drug (anti-inflammation)
Pseudo substrate competitive inhibitor
● Protease inhibitor
Alzheimer's disease
Plaques in brain contains protein inhibitor
● HIV protease is critical to life cycle of HIV
HIV protease (homodimer):
subunit 1
↑inhibitor is used to treat AIDS
As
p
→ Human aspartyl protease:
(monodimer)
subunit 2
As
p
Symmetry
domain 1 domain 2 Not
As
p
symmetry
As
p Juang RH (2004) BCbasics
HIV protease vs Aspartyl protease
HIV Protease inhibitor is used in treating AIDS
↓ HIV protease (homodimer)
subunit 1
Asp
domain 1
Asp
subunit 2
Symmetric
dimer
Asp
domain 2
Asp
Asymmetric
monomer
↑Aspartyl protease (monomer)
Juang RH (2004) BCbasics