Medical Enzymology

By

Amr S. Moustafa, M.D.; Ph.D.

Assistant Prof. & Consultant, Medical Biochemistry Dept.

College of Medicine, KSUamrsm@hotmail.com

Michaelis-Menten Equation

E + S ES E + P

v° =

Km: Michaelis constant = (k-1 + k2) / k1

k1

K-1

k2

Vmax [S]Km + [S]

Michaelis-Menten Kinetics

Zero and First Order Reactions

Lineweaver-Burk Plot

= + 1v°

Km

Vmax [S]1

Vmax

Inhibition of Enzyme Activity

Inhibitor: The velocity of the reaction

Reversible or irreversible

Competitive or noncompetitive

Competitive Inhibition -1

Inhibitors: Structural similarity to SBind to S-binding site (compete with S)ES or EI complexes [S] overcomes the inhibition

Km But, no effect on Vmax

Competitive Inhibition -2

Statin Drugs, e.g., Simvastatin (Zocor)

Competitive Inhibition -3

Noncompetitive Inhibition -1

Inhibitors: No structural similarity to SBind to different (allosteric) siteES or EI or ESI complexes [S] cannot overcome the inhibition

Vmax But, no effect on Km

Noncompetitive Inhibition -2

Noncompetitive Inhibition -3

Noncompetitive Inhibition -4

Lead and Ferrochelatase

Insecticides and actylcholinesterase

Covalent and irreversible

Therapeutic Potential of Enzyme Inhibition

β-Lactam antibiotics, e.g., Penicillin

Angiotensin-converting enzyme (ACE) inhibitors, e.g., Captopril

Statin drugs as antihyperlipidemic