Enzyme KineticsAnd

Inhibition

Biochemistry 2nd ed, Voet/Voet

Substrate Specificity

Substrate and Activesite are complementary

chemically.

hydrophobic

Biochemistry 2nd ed, Voet/Voet

Stereospecificity

Only one enantiomerwill fit correctly into

active site

Allosteric and Feedback Regulation of ACTase

ATP activates Enzyme

CTP inactivates Enzyme

Biochemistry 2nd ed, Voet/Voet

Lineweaver-Burke Plot

Competitive Inhibition

From Biochemistry, Matthews/VanHolde

Because the inhibitorcompetes with substrate,

Km is changed.

Vmax stays the samebecause ES EP

is same rateonce S is bound.

Competitive Inhibition

Non-Competitive Inhibition

From Biochemistry, Matthews/VanHolde

Because the inhibitorchanges the rate of

catalysis by inducing a conformational change in E, Vmax is changed.

Km stays the same because S binding is not

affected by I binding.

Non-competitive Inhibition

Mixed Inhibition

Inhibitor binds remotely from the active site but

changes both catalysis rate (Vmax) and substrate binding (Km)

CH

CH

O

CH

CH

CH2O

OHO

O-

O

P

C

C

C

N

NH

CN

CH

N

NH2

O

C

C

C

N

NH

CC

N

N

O CH3

CH2 CH2 CH3

OCH2CH3

SN

N

CH3

O

O

Phosphodiesterase Inhibitor

Smooth muscle cells relax:

NO. nitrous oxide ~ neurotransmitter

cGMP ~ cyclic GMP (top structure)

Intracellular Ca2+ concentration decreases

Muscle relaxation

If can get smooth muscle of blood vesselwalls to relax, then treat angina and high blood pressure

cGMP

Phosphodiesterases (PDE) cleave cGMP to GMPcausing muscle contraction

Inhibit PDE 5 (isozyme prevalent in vascular tissue)At least 9 isozymes.

Competitive inhibitor of PDE developed and marketedDidnt work well