Competitive Inhibition Product COO Substrate Competitive Inhibitor Succinate

Competitive Inhibition Product C-OO- Substrate Competitive Inhibitor Succinate Glutarate Malonate C-OO- C-H H-C-H C-OO- H-C-H Oxalate C-OO- H-C-H C-OO- Succinate Dehydrogenase Adapted from Kleinsmith & Kish (1995) Principles of Cell and Molecular Biology (2 e) p. 49

Sulfa Drug Is Competitive Inhibitor Domagk (1939) Para-aminobenzoic acid (PABA) H 2 N- -COOH Bacteria needs PABA for the biosynthesis of folic acid Folic acid Precursor H 2 N- -SONH 2 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 (5 e) 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 protease (homodimer): subunit 1 ↑inhibitor is used to treat AIDS Asp → Human aspartyl protease: (monodimer) subunit 2 Asp domain 1 domain 2 Asp Symmetr Not symmetry 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 Asp domain 2 Asp Symmetric dimer Asymmetric monomer ↑Aspartyl protease (monomer) Juang RH (2004) BCbasics