Welcome to Introduction to Bioinformatics Wednesday, 16 October Metabolic modeling

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Welcome toIntroduction to BioinformaticsWednesda
y, 16 OctoberMetabolic modeling

• Table of Contents
• First exam Rules of the game
• Sep 27, SQ4 Write subroutine to print score
  array
• PS1M.8 Probability of evolution

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Trypanosoma bruceiCausative agent of sleeping
sickness
Life Cycle
Central Nervous SystemDeath
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Trypanosoma bruceiDependence on glycolysis
Treatment
Arsenate(AsO4 Asi) Competitivewith Pi
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Trypanosoma bruceiDependence on glycolysis
Treatment
Something more specific?
inhibitor1
Choice 1Starve the cell
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Trypanosoma bruceiDependence on glycolysis
Treatment
Something more specific?
Choice 1Starve the cell
Choice 2Stuff the cell
pyruvate
inhibitor2
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Trypanosoma bruceiTest ideas for inhibitors
inhibitor1
We knowcharacteristicsof enzymes
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Characteristics of enzymesAnalogy of
radioactivity
How often does 32S appear?
1/20 of an atom per day?
X atoms of 32P
__atoms of 32S per day

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Characteristics of enzymesAnalogy of
radioactivity
Which quantity is an intrinsic characteristic?
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Characteristics of enzymesAnalogy of
radioactivity
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Characteristics of enzymesChemical reactions
AMP-P-As
AMP-P Asi
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Characteristics of enzymesChemical reactions
AMP-P-As
AMP-P Asi
AMP-P-As
dAMP-P / dt
concentration
rate of change

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Characteristics of enzymesChemical reactions
AMP-P-As
AMP-P Asi
AMP-P-As
concentration
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Characteristics of enzymesChemical reactions
AMP-P-As
AMP-P Asi
AMP-P-As
concentration
dS / dt
kS
A differential equation
S0 (k) e -k(t-to)
-k S0 e -k(t-to)
-k S
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Characteristics of enzymesChemical reactions
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Characteristics of enzymesChemical reactions
S
S0
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Characteristics of enzymesChemical reactions
S0
?t
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Characteristics of enzymesChemical reactions
(Program)
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Characteristics of enzymesChemical reactions
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Characteristics of enzymesChemical reactions
?t dS / dt
S
S0
S0
Use average of Slope0 and Slope1
?t
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Characteristics of enzymesChemical reactions
?t dS / dt
S
S0
Slope0 -kS0
S1
?t dS / dt
S0
Slope1 -kS1
S0
Use average of Slope0 and Slope1
Runge-Kutta method
?t
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Characteristics of enzymesEnzymatic reactions
inhibitor1
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Characteristics of enzymesEnzymatic reactions
Glucose-6-phosphate
Fructose-6-phosphate
G6P
concentration
k ? 0
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Characteristics of enzymesEnzymatic reactions
G6P E
G6PE
F6PE
F6P E
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Characteristics of enzymesEnzymatic reactions
k1f
k1cf
G6P E1
E1-complex
F6P E1
k1r
k1cr
d
dG6P / dt dE1 / dt dE1-complex / dt
dF6P / dt
-G6P E1 k1f E1-complex k1r
-G6P E1 k1f E1-complex k1r
E1-complex k1cf - F6P E1 k1cr
G6P E1 k1f - E1-complex k1r-
E1-complex k1cf F6P E1 k1cr
E1-complex k1cf - F6P E1 k1cr
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Characteristics of enzymesEnzymatic reactions
k1f
k1cf
G6P E1
E1-complex
F6P E1
k1r
k1cr
k1if
I E1
E1-I-complex
k1ir
- G6P E1 k1f E1-complex
k1rE1-complex k1cf - F6P E1 k1cr - I
E1 k1if E1-I-complex k1ir
dE1 / dt dI / dt d E1-I-complex /
dt
d
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Characteristics of enzymesEnzymatic reactions
k1f
k1cf
G6P E1
E1-complex
F6P E1
k1r
k1cr
d
dG6P / dt dE1 / dt dE1-complex / dt
dF6P / dt
-G6P E1 k1f E1-complex k1r
-G6P E1 k1f E1-complex k1r
E1-complex k1cf - F6P E1 k1cr
G6P E1 k1f - E1-complex k1r-
E1-complex k1cf F6P E1 k1cr
E1-complex k1cf - F6P E1 k1cr
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Characteristics of enzymesEnzymatic reactions
k1f
k1c
G6P E1
E1-complex
F6P E1
k1r
dE1-complex / dt dF6P / dt
G6P E1 k1f - E1-complex k1r-
E1-complex k1c F6P E1 k1cr
E1-complex k1c - F6P E1 k1cr
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Characteristics of enzymesEnzymatic reactions
k1f
k1cf
G6P E1
E1-complex
F6P E1
k1r
G6P E1 k1f E1-complex k1c -
E1-complex k1r
dE1-complex / dt dF6P / dt
G6P (Etotal-E1-complex) k1f
E1-complex (k1c - k1r)
G6P E1 k1f - E1-complex k1r-
E1-complex k1c F6P E1 k1cr
E1-complex k1c - F6P E1 k1cr
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Characteristics of enzymesEnzymatic reactions
k1f
k1cf
G6P E1
E1-complex
F6P E1
k1r
G6P E1 k1f E1-complex k1c -
E1-complex k1r
dF6P / dt
G6P (Etotal-E1-complex) k1f
E1-complex (k1c - k1r)
G6P Etotal k1f
G6P Etotal
G6P (k1c - k1r) G6P (k1c
- k1r)/k1f
E1-complex

E1-complex k1c - F6P E1 k1cr
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Characteristics of enzymesEnzymatic reactions
k1f
k1cf
G6P E1
E1-complex
F6P E1
k1r
dF6P / dt E1-complex k1c
G6P Etotal k1cG6P (k1c - k1r)/k1f


G6P Etotal k1c G6P Km


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Characteristics of enzymesEnzymatic reactions
k1f
k1cf
G6P E1
E1-complex
F6P E1
k1r
dF6P / dt E1-complex k1c
G6P Etotal k1cG6P (k1c - k1r)/k1f


G6P Etotal k1c G6P Km


G6P Etotal k1c G6P Km
Max dF6P / dt (Vmax)
Etotal k1c
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Characteristics of enzymesEnzymatic reactions
k1f
k1cf
G6P E1
E1-complex
F6P E1
k1r
G6P VMax G6P Km
dF6P / dt
S VMax S Km
dproduct / dt
v (velocity)
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