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

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Discussion Overview

The discussion revolves around the implications of setting the rate constant $k_2$ to zero in the context of enzyme kinetics, specifically examining the uptake equation and its relationship to the Michaelis-Menten model. Participants explore the mathematical modeling of enzyme-substrate interactions and the resulting differential equations.

Discussion Character

  • Technical explanation
  • Mathematical reasoning
  • Debate/contested

Main Points Raised

  • One participant questions how the uptake $r(u)$ would change when $k_2 = 0$ and whether this necessitates a complete re-evaluation of the model.
  • Another participant suggests that the non-dimensionalization process may need to be reworked due to the change in $k_2$.
  • A participant presents the Michaelis-Menten uptake equation and its parameters, indicating that $K_m$ is defined as $K_m=\dfrac{k_{-1}+k_2}{k_1}$.
  • There is a mention of the maximum velocity $Q_{s_0}=k_2e_0s_0$ in the context of the Michaelis-Menten model.
  • One participant expresses interest in plotting the Michaelis-Menten uptake in Mathematica, indicating a practical application of the discussed concepts.

Areas of Agreement / Disagreement

Participants express differing views on the implications of setting $k_2 = 0$, with some suggesting significant changes to the model while others focus on the mathematical formulations. The discussion remains unresolved regarding the overall impact on the uptake equation and the necessity of reworking the non-dimensionalization.

Contextual Notes

Limitations include the dependence on the definitions of the rate constants and the potential need for adjustments in the mathematical modeling due to the change in $k_2$. The discussion does not resolve the mathematical steps or assumptions involved in the modeling process.

Dustinsfl
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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
$$
\frac{du}{d\tau} = -r(u) = -u\frac{A + Bu}{C + u + Du^2}.
$$
 
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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
 

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