Is the Uptake Equation Different When $k_2 = 0$?

  • Context: MHB 
  • Thread starter Thread starter Dustinsfl
  • Start date Start date
Click For Summary
SUMMARY

The discussion centers on the implications of setting $k_2 = 0$ in the context of enzyme kinetics, specifically within the Michaelis-Menten framework. When $k_2 = 0$, the differential equations governing the system change significantly, necessitating a re-evaluation of the uptake equation $r(u)$. The Michaelis-Menten rate of uptake is defined as $R_0 = \frac{Q_{s_0}}{K_m+s_0}$, where $K_m = \frac{k_{-1}+k_2}{k_1}$ and $Q_{s_0} = k_2 e_0 s_0$. The discussion concludes with a query on how to visualize these equations using Mathematica.

PREREQUISITES
  • Understanding of enzyme kinetics and the Michaelis-Menten model
  • Familiarity with differential equations and the Law of Mass Action
  • Knowledge of non-dimensionalization techniques in mathematical modeling
  • Proficiency in using Mathematica for plotting and visualizing mathematical functions
NEXT STEPS
  • Explore the derivation of the Michaelis-Menten equation in detail
  • Learn about the implications of varying enzyme constants ($k_1$, $k_{-1}$, $k_2$, $k_3$, $k_{-3}$) on reaction rates
  • Investigate numerical methods for solving differential equations relevant to enzyme kinetics
  • Study advanced plotting techniques in Mathematica to visualize enzyme kinetics models
USEFUL FOR

This discussion is beneficial for biochemists, mathematical biologists, and researchers involved in enzyme kinetics modeling and analysis, as well as anyone interested in computational biology and mathematical visualization techniques.

Dustinsfl
Messages
2,217
Reaction score
5
The question I have is: when $k_2 = 0$ sketch the uptake $r(u)$ as a function of $u$ and compare it with the Michaelis-Menten uptake.
If $k_2 = 0$, wouldn't that change everything significantly? Does that mean re-do everything with $k_2 = 0$.
Is the Michaelis-Menten uptake just Michaelis constant?$$
S + E \underset{k_{-1}}{\overset{k_1}{\rightleftharpoons}} C_1 \xrightarrow{k_2} E + P,
$$
$$
S + C_1 \underset{k_{-3}}{\overset{k_3}{\rightleftharpoons}} C_2\xrightarrow{k_4} C_1 + P
$$
Let $s = $, $e = [E]$, $c_1 = C_1$, $c_2 = [C_2]$, and $p = [P]$.
Then by the Law of Mass action, we can write down the differential equation model as:
\begin{align}
\frac{ds}{dt} =& -k_1es + (k_{-1} - k_3s)c_1 + k_{-3}c_2,\\
\frac{dc_1}{dt} =& k_1se - (k_{-1} + k_2 + k_3s)c_1 + (k_{-3} + k_4)c_2,\\
\frac{dc_2}{dt} =& k_3sc_1 - (k_{-3} + k_4)c_2,\\
\frac{de}{dt} =& -k_1se + (k_{-1} + k_2)c_1,\\
\frac{dp}{dt} =& k_2c_2 + k_4c_2
\end{align}
The initial conditions for the differential equation model are
$$
s(0) = s_0,\quad e(0) = e_0,\quad c_1(0) = c_2(0) = p(0) = 0.
$$
Since the enzyme is the catalyst, the enzyme is conserved by adding equations 2, 3, and 4.
$$
\frac{de}{dt} + \frac{dc_1}{dt} + \frac{dc_2}{dt} = 0\Rightarrow e(t) + c_1(t) + c_2(t) = e_0
$$
Then $e(t) = e_0 - c_1(t) - c_2(t)$.
Since $dp/dt$ is uncoupled, we can directly solve for $p(t)$.
$$
\int dp = \int (k_2c_1 + k_4c_2)dt\Rightarrow p(t) = k_2\int c_1dt + k_4\int c_2dt
$$
The only equations left to solve for are equations 1, 2, and 3 which are
\begin{align}
\frac{ds}{dt} =& -k_1e_0s + (k_{-1} + k_1s - k_3s)c_1 + (k_1s + k_{-3})c_2,\notag\\
\frac{dc_1}{dt} =& k_1e_0s - (k_{-1} + k_2 +k_1s +k_3s)c_1 + (k_{-3} + k_4 - k_1s)c_2,\notag\\
\frac{dc_2}{dt} =& k_3sc_1 - (k_{-3} + k_4)c_2,\notag
\end{align}
after substituting $e(t) = e_0 - c_1(t) - c_2(t)$.
By making the substitutions
\begin{alignat*}{4}
\tau &= k_1e_0t, & u &= \frac{s}{s_0}, & v_1 &= \frac{c_1}{e_0}, & v_2 &= \frac{c_2}{e_0},\notag\\
a_1 &= \frac{k_{-1}}{k_1s_0}, &\quad a_2 &= \frac{k_2}{k_1s_0}, &\quad a_3 &= \frac{k_3}{k_1}, &\quad a_4 &= \frac{k_{-3}}{k_1s_0},\notag\\
a_5 &= \frac{k_4}{k_1s_0}, & \epsilon &= \frac{e_0}{s_0}
\end{alignat*}
we can non-dimensionalize then model as
\begin{align}
\frac{du}{d\tau} =& -u + (u -a_3u + a_1)v_1 + (a_4 + u)v_2 = f(u,v_1,v_2),\notag\\
\epsilon\frac{dv_1}{d\tau} =& u - (u + a_3u + a_1 + a_2)v_1 +(a_4 + a_5 - u)v_2 = g_1(u,v_1,v_2),\notag\\
\epsilon\frac{dv_2}{d\tau} =& a_3uv_1 - (a_4 + a_5)v_2 = g_2(u,v_1,v_2).\notag
\end{align}
The initial conditions for the dimensionless model are
$$
u(0) = 1,\quad v_1(0) = v_2(0) = 0.
$$
Just as in class this model is a single perturbation for $0 < \epsilon\ll 1$.
Solving for $v_1$ and $v_2$, we obtain
$$
v_1 = \frac{u}{a_1 + a_2 + u + a_3u^2(a_4 + a_5)^{-1}} \quad\text{and}\quad v_2 = \frac{a_3uv_1}{a_4 + a_5}.
$$
Then
$$
f(u,v_1(u),v_2(u)) = \frac{du}{d\tau} = -u\frac{a_2 + a_3a_5u(a_4 + a_5)^-1}{a_1 + a_2 + u + a_3u^2(a_4 + a_5)^{-1}} = -r(u)
$$
is the uptake equation for $u$.
Let$A = a_2$, $B = a_3a_5(a_4 + a_5)^{-1}$, $C = a_1 + a_2$, and $D = a_3(a_4 + a_5)^{-1}$.
Then
$$
\frac{du}{d\tau} = -r(u) = -u\frac{A + Bu}{C + u + Du^2}.
$$
 
Last edited:
Physics news on Phys.org
Would it be a simply substitution or would the non-dimensionalization have to be re-worked?

$$
S + E \underset{k_{-1}}{\overset{k_1}{\rightleftharpoons}} C_1,
$$
$$
S + C_1 \underset{k_{-3}}{\overset{k_3}{\rightleftharpoons}} C_2\xrightarrow{k_4} C_1 + P
$$
Let $s = $, $e = [E]$, $c_1 = C_1$, $c_2 = [C_2]$, and $p = [P]$.
Then by the Law of Mass action, we can write down the differential equation model as:
\begin{align}
\frac{ds}{dt} =& -k_1es + (k_{-1} - k_3s)c_1 + k_{-3}c_2,\\
\frac{dc_1}{dt} =& k_1se - (k_{-1} + 0 + k_3s)c_1 + (k_{-3} + k_4)c_2,\\
\frac{dc_2}{dt} =& k_3sc_1 - (k_{-3} + k_4)c_2,\\
\frac{de}{dt} =& -k_1se + (k_{-1} + 0)c_1,\\
\frac{dp}{dt} =& 0 + k_4c_2
\end{align}
The initial conditions for the differential equation model are
$$
s(0) = s_0,\quad e(0) = e_0,\quad c_1(0) = c_2(0) = p(0) = 0.
$$
Since the enzyme is the catalyst, the enzyme is conserved by adding equations 2, 3, and 4.
$$
\frac{de}{dt} + \frac{dc_1}{dt} + \frac{dc_2}{dt} = 0\Rightarrow e(t) + c_1(t) + c_2(t) = e_0
$$
Then $e(t) = e_0 - c_1(t) - c_2(t)$.
Since $dp/dt$ is uncoupled, we can directly solve for $p(t)$.
$$
\int dp = \int (0 + k_4c_2)dt\Rightarrow p(t) = 0 + k_4\int c_2dt
$$
The only equations left to solve for are equations 1, 2, and 3 which are
\begin{align}
\frac{ds}{dt} =& -k_1e_0s + (k_{-1} + k_1s - k_3s)c_1 + (k_1s + k_{-3})c_2,\notag\\
\frac{dc_1}{dt} =& k_1e_0s - (k_{-1} + 0 +k_1s +k_3s)c_1 + (k_{-3} + k_4 - k_1s)c_2,\notag\\
\frac{dc_2}{dt} =& k_3sc_1 - (k_{-3} + k_4)c_2,\notag
\end{align}
after substituting $e(t) = e_0 - c_1(t) - c_2(t)$.
By making the substitutions
\begin{alignat*}{4}
\tau &= k_1e_0t, & u &= \frac{s}{s_0}, & v_1 &= \frac{c_1}{e_0}, & v_2 &= \frac{c_2}{e_0},\notag\\
a_1 &= \frac{k_{-1}}{k_1s_0}, &\quad a_2 &= \frac{0}{k_1s_0}=0, &\quad a_3 &= \frac{k_3}{k_1}, &\quad a_4 &= \frac{k_{-3}}{k_1s_0},\notag\\
a_5 &= \frac{k_4}{k_1s_0}, & \epsilon &= \frac{e_0}{s_0}
\end{alignat*}
we can non-dimensionalize then model as
\begin{align}
\frac{du}{d\tau} =& -u + (u -a_3u + a_1)v_1 + (a_4 + u)v_2 = f(u,v_1,v_2),\notag\\
\epsilon\frac{dv_1}{d\tau} =& u - (u + a_3u + a_1 + 0)v_1 +(a_4 + a_5 - u)v_2 = g_1(u,v_1,v_2),\notag\\
\epsilon\frac{dv_2}{d\tau} =& a_3uv_1 - (a_4 + a_5)v_2 = g_2(u,v_1,v_2).\notag
\end{align}
The initial conditions for the dimensionless model are
$$
u(0) = 1,\quad v_1(0) = v_2(0) = 0.
$$
Just as in class this model is a single perturbation for $0 < \epsilon\ll 1$.
Solving for $v_1$ and $v_2$, we obtain
$$
v_1 = \frac{u}{a_1 + 0 + u + a_3u^2(a_4 + a_5)^{-1}} \quad\text{and}\quad v_2 = \frac{a_3uv_1}{a_4 + a_5}.
$$
Then
$$
f(u,v_1(u),v_2(u)) = \frac{du}{d\tau} = -u\frac{0 + a_3a_5u(a_4 + a_5)^-1}{a_1 + 0 + u + a_3u^2(a_4 + a_5)^{-1}} = -r(u)
$$
is the uptake equation for $u$.
Let$A = a_2=0$, $B = a_3a_5(a_4 + a_5)^{-1}$, $C = a_1 + a_2$, and $D = a_3(a_4 + a_5)^{-1}$.
Then
$$
\frac{du}{d\tau} = -r(u) = -u\frac{Bu}{C + u + Du^2}.
$$
 
Michaelis-Menten uptake

So the Michaelis-Menten rate of uptake is
$$
R_0 = \frac{Q_{s_0}}{K_m+s_0}
$$
where $K_m=\dfrac{k_{-1}+k_2}{k_1}$ and $Q_{s_0}=k_2e_0s_0$

Q is the max velocity K_m is the Michaelis constant.

How can I plot this in Mathematica?
 
Re: Michaelis-Menten uptake

​Solved
 

Similar threads

  • · Replies 2 ·
Replies
2
Views
2K
  • · Replies 5 ·
Replies
5
Views
2K
  • · Replies 9 ·
Replies
9
Views
5K
  • · Replies 7 ·
Replies
7
Views
3K
  • · Replies 6 ·
Replies
6
Views
3K
  • · Replies 3 ·
Replies
3
Views
2K
  • · Replies 101 ·
4
Replies
101
Views
10K
  • · Replies 1 ·
Replies
1
Views
1K
  • · Replies 36 ·
2
Replies
36
Views
6K
  • · Replies 1 ·
Replies
1
Views
2K