Biochemical Kinetics

Chemical Kinetics
Elementary Reactions R ——> P Reaction Intermediates R ——> I1 ——> I2 ——> P
When number of molecules are large, the system will be deterministic. We can use ODE based formulations of chemical kinetics But in a single cell, number of each species can be very low (even in tens) ODE based formulations can be used if you compare an ensemble of cells

Rate Equations
aA + bB ——> P Following the Law of Mass Action Rate of formation of P, dP/dt = k[A]a[B]b K = rate constant Order of Reaction = a + b

Reaction kinetics: 1st order reactions
A k1 B (+ C)

d[A] = k1[A] Rate: dt
d[A] Rewriting: = k1dt [A]

[A]

••

••

t

Integration gives:

1 d[A] = − ktdt [A] 0 0

t

t

So: ln[A]t – ln[A]0 = -kt

or: ln

[ A ]t = -kt [ A]0

x

[ A ]t = -kt ln [ A]0

ln[A] t ln[A]t

x x

slope = - k x x t

The halflife, t1/2, is defined as the time that is needed to reduce the concentration of the reactant to 50% of its original value. In formula:
1 / 2[A]0 =-kt1/2 so ln [A]0
t 1/ 2 ln 2 0.693 = = k k

Reaction kinetics: 2nd order reactions
A+B k2 P

d[A ] d[B] d[P] ==+ = k 2 [A][ B] dt dt dt

take [P] = x, then [A] = [A]0 – x and [B] = [B]0 – x
d[P] dx = k 2 [A][ B] = k2([A]0-x)([B]0-x) = The rate then becomes: ν = dt dt

so

1 dx = k 2 dt ([A]0 - x)([B]0 - x)

Do, substitutions: [A]0 – x = z; [B]0 – x = [B]0 – [A]0 + z; dx = - dz; Do integration for,

− dz = k .dt z.([ B]0 − [ A]0 + z )
[A]0 [B] 1 = k 2t ln Integration gives: [B]0 - [A]0 [A][ B]0

[B] Plotting ln against t gives a straight line with slope k2([B]0-[A]0) [A]

Special cases:
• [A]0>>[B]0 (pseudo-first order kinetics)

Example: A + H2O

B, reaction happening in water in which k'=k2[H2O]

d [ B] = k2 [ A][ H 2O ] = k '[ A] dt

This is a pseudo-first order reaction, since [H2O] is constant. The second-order rate constant k2 can be calculated from k' and [H2O]. In a dilute aqueous solution, [H2O]=55 M.

Special cases:
2.A B

1 d [ A] d [ B ] = = k2 [ A]2 2 dt dt
1 1 = 2k 2 t Integration gives: [A]t [A]0

1 1 Plotting of against t gives 2k2 as the slope. [A ]t [A]0

Reversible reactions
A k1 k-1
[A]0

B
xe

[A]t [B]t

On t = 0: [A] = [A]0 [B] = 0 t = t: [A] = [A]0-x [B] = x

t

dx = k1[A] – k-1[B] = k1([A]0 – x) – k-1x = k1[A]0 – (k1 + k-1)x dt
k1[A ]0 - (k1 + k -1 ) x = -(k1 + k -1 ) t Integration gives: ln k1[A]0

At equilibrium, the net reaction rate = 0, so: k1[A]e = k-1[B]e = k-1xe

There is an equilibrium constant: so: [A]0 = x e 1 + k −1
k1

xe k1 [B]e = = K= k -1 [A ]e [A ]0 - x e

Combining two equations:

xe - x ln = -(k1 + k -1 ) t xe

xe - x Determination of (k1 + k-1) by plotting ln xe

against t

A

k1 k-1

B → C
k2

d [ B] = k1.[ A] − k−1.[ B] − k2 .[ B ] dt
Kinetics is complicated, so one common approach is to consider steady state

d[B] =0 dt

k1[A]= k-1[B] + k2[B] = (k-1 + k2)[B]

So the rate equation for synthesis of C becomes:

ν = k2[B] =

k1k 2 [A] k −1 + k 2

Does such steady state exist?

k1k 2 [A] v= k −1 + k 2

If, k2 >> k-1

v = k1[ A]

k1k 2 [A] v= k −1 + k 2

If k2 << k-1 and k1

k1 v = k2 . [ A] = k2 .K eq [ A] k−1