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10 Equations in Biology:

Michaelis-Menten Kinetics

[E ]t1 [E ]t kf [E ]t [S]t kr [ES]t kcat [ES]t


[S]t1 [S]t kf [E ]t [S]t kr [ES]t
[ES]t1 [ES]t kf [E ]t [S]t kr [ES]t kcat [ES]t
[P ]t1 [P ]t kcat [ES]t
Outline
1. Brief intro to enzyme kinetics

2. From intuitive conceptions to a formal model

3. Building interactive models in Excel

4. From a mathematical model to biological insights


Intro to Enzyme Kinetics
kf kcat
E+S ES E+P
kr

Variables Parameters
[E]: free enzyme molecules kf , kr , kcat : reaction rates
[S]: free substrate molecules
[ES]: enzyme-substrate complexes
[P]: free product molecules
Writing Word Equations
A word equation is a qualitative description
of the systems major processes

Goal: help students express their proto-


mathematical understanding of a system
before introducing formal math.

Example: Balancing a checkbook


$ in checking $ in checking deposits withdrawals
account on =
Sept. 1st
?
account on
Aug. 1st
+ made in
August
made in
August
Word Equations for
Enzyme Kinetics Model

# of free S # of ES
# of free S # of free S
molecules complexes
molecules = molecules binding to + splitting
at time t +1 at time t
free E into E + S

Write similar word equations for the other 3 variables.


Translate Word
Equations into
Formal Equations
# of free S molecules
at time t = [S]t
conc. of enzyme-
substrate complexes

# of ES complexes
splitting into E + S = kr [ES]t
conc. of free enzyme
conc. of free substrate
# of free S molecules
binding to free E = kf [E]t [S]t
by Law of Mass Action
Formal Equations for
Enzyme Kinetics Model

[E ]t1 [E ]t kf [E ]t [S]t kr [ES]t kcat [ES]t


[S]t1 [S]t kf [E ]t [S]t kr [ES]t
[ES]t1 [ES]t kf [E ]t [S]t kr [ES]t kcat [ES]t
[P ]t1 [P ]t kcat [ES]t
Modeling in Excel
Why Excel rather than more powerful tools?

easily available on most campuses

widely used = transferable proficiency

nonthreatening to students

makes students work directly with the equations:


no dodges via the user interface!
Implementing a
Model in Excel
1. Write a series of recursion equations.

2. Set up Excel sheet with time in Column A,


other variables in next columns.

3. Enter and name model parameters;


enter variables starting values.
4. Enter recursion equations for each variable.

5. Copy and paste for subsequent time steps.


6. Graph results appropriately.
Structured Exploration:
Understand the Model
1. How would you measure the reactions velocity?
How does velocity change over the course of the
reaction, and why?

2. How does each rate constant influence


the reactions velocity? Why?
Further Exploration
Enzyme Kinetics Multiple Runs.xlsx

What happens to velocity


as [S]0 increases? Why?

Estimate vmax
for this enzyme.
Further Exploration
Biological interpretation of KM?

Characterize the Michaelis-


Menten curves of enzymes
w/low, medium, and high KM.
K M (kr kcat ) / kf
Estimating
Reaction
Constants
What is the shape of
the M-M curve?

Nonlinear regression:
Fit the appropriate
curve to the M-M plot
by minimizing the sum
of squared residuals.

Use built-in scrollbars


to adjust estimates
of vmax and Km.
Estimating Reaction Constants:
Linear Methods
Goal: Convert the Michaelis-Menten vmax [S]
equation into a form that v
K M [S]
linearizes the best-fit curve.

Example
Lineweaver-Burk plot:
1/v vs. 1/[S]0
Formula = ?

Should be able to write


similar formulas for
other plots (H-W, E-H)
Estimating Reaction Constants:
Evaluating Diff. Methods
On what basis might one method
be considered better than others?

Each methods
sensitivity to
estimation error?

Each methods
ability to detect
such error?
Beyond Simple Enzyme Kinetics

How could you modify the model to describe

Influx or efflux of reaction components?

Reversible, competing, or multi-step reactions?


Totally different biological systems
(pop. dynamics, epidemiology, pharmacokinetics, )?
Preview: Agent-Based Models

Simulate &
visualize behavior
of each indiv.
molecule

Focus of next
weeks seminar
(Nernst equation)
Take-home message

Build equations to clarify each terms


meaning and identify key assumptions

Explore models to test understanding


of a system, and to ground abstract
discussions

Lesson structure: what aspects of this


seminar did you find most/least crucial?

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