Natchanok Chaisongkram

Ruel Cedeno
Thitapond Nulek
Case III: Non-competitive Inhibition
k1

ES

k1

E S

k2

E S E P
k3

E I inactive

EI

k3

k4

E I S

k4
k5

E S I

k5

I E S inactive
I E S inactive

We need to find the rate law for the rate of product formation
r p k2 E S equation1
To do this, assume that the reactions containing inactive component are in equilibrium;
that is, the rate of forward reaction is equal to the rate of backward reaction.
k3 E I k3 E I

k3 E I
E I
k3

k4 E I S k4 I E S

E I S

k5 E S I k5 I E S

equation 2

k4 E I S

k 4

equation 3

Substitute the expression for E I in equation 2 to equation 3

E I S

k4 E I S

k4

k3 E I
S
k3

k4
k4

k3 k 4 E I S

equation 4
k 3 k 4

Since E S is an active component, rE S 0

rE S k1 E S k 1 E S k 2 E S k5 E S I k5 I E S 0

Since k5 E S I k 5 I E S , they will cancel out

rE S k1 E S k 1 E S k 2 E S

E S

Since the total amount of enzyme is constant

ET E E S E I E

I S

k1 E S

(equation 5)
k1 k2

Combine equations 2,4, and 5

ET E

k1 E S

Factor out E

ET E

k 1 k 2

k1 S
k1 k2

k3 E I
k3
k3 I

ET
k3 I

k1 S

k3

k3 k4 E I S
k3 k4

k3 k4 I S

k3 k4

k3 k 4 I S

k 1 k 2
k3
k3 k4

Now, combine equations1,5, and 6

equation 6

k1 E S

k 1 k 2

r p k2 E S k2

k1 k2 ET S

k1 k2

rp

k1k2 ET S

k3 k1 k 2 I

k1 k2 k1 S

k 3

k1 S

k 1 k 2

k3 I
k3

k3 k4 I S

k3 k4

k3 k4 k 1 k2 I S
k 3 k 4

Now, we will express the rate law in terms of vmax , K m and K I .

Let K m
rp

k
k1 k2 k4

assuming dissociation constant of substrate is the same and 3 K I

k1
k4
k3

k 1 k 2

k1

rp

rp

k1 S
k1

k2 ET S

k1 k2
I k1 k 2
I S

k1 k3
k1 k3 k4

k 3 k4
k3

k2 ET S
Km I

Km S

KI

Km I S
K I Km

k2 ET S

Km S

K I

K m S

k2 ET
Km S

S
Km I I S

k2 ET S

K m S

KI

K I

KI
vmax S

K m S

I
1

KI