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230 SEcTIoN II Pharmacology ` PHARMACOLOGY—PHARMACOKINETICS ANd PHARMACOdYNAMICS Pharmacology ` PHARMACOLOGY—PHARMACOKINETICS ANd PHARMACOdYNAMICS

` PHARMACOLOGY—PHARMACOKINETICS ANd PHARMACOdYNAMICS

Enzyme kinetics
Noncompetitive inhibitor
Michaelis-Menten K m is inversely related to the affinity of the [S] = concentration of substrate; V = velocity.
Competitive inhibitor (reversible)
kinetics enzyme for its substrate. V 1 Uninhibited
Saturation
V max is directly proportional to the enzyme V 1
concentration. Velocity (V) − K max m 1 K = [S] at ⁄ V
V
Most enzymatic reactions follow a hyperbolic ⁄ V max 1 max m max
curve (ie, Michaelis-Menten kinetics); [S]
however, enzymatic reactions that exhibit a K m [S]
sigmoid curve usually indicate cooperative Effects of enzyme inhibition Saturation
Uninhibited
Saturation
kinetics (eg, hemoglobin). V max 1 slope = K m
V
Velocity (V) ⁄ V Competitive inhibitor (reversible)
V
1 Velocity (V) V max 1 K = [S] at ⁄ V
max
max
m
− K m ⁄ V max max V max
K 1 [S] Noncompetitive inhibitor
K m [S]
[S]
m
Lineweaver-Burk plot The closer to 0 on the Y-axis, the higher the 1 Noncompetitive inhibitor
Uninhibited
K
V max . 1 V Competitive inhibitor m
slope =
1
The closer to 0 on the X-axis, the higher the K m . − K V 1 Uninhibited V max
The higher the K m , the lower the affinity. m V max
1
Competitive inhibitors cross each other, 1 [S]
[S]
whereas noncompetitive inhibitors do not. Effects of enzyme inhibition
Noncompetitive inhibitor
Competitive inhibitor
1 Noncompetitive inhibitor
Kompetitive inhibitors increase K m . V Competitive inhibitor (reversible)
Uninhibited
1
V Uninhibited
1
− K 1
m 1 V max
[S]
1
[S]
Competitive Competitive
inhibitors, inhibitors, Noncom
Saturationpetitive
reversible irreve Vrsible inhibitors
Velocity (V)
max
Resemble substrate Yes Yes ⁄ V max Competitive inhibitor (reversible)
No
Overcome by  [S] Yes No Noncompetitive inhibitor
No
K [S]
Bind active site Yes Yes m No
Unchanged  
Effect on V max
 Unchanged Unchanged
Effect on K m
Pharmacodynamics  potency  efficacy  efficacy

FAS1_2019_05-Pharmacology.indd 230 11/7/19 4:08 PM