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Friday, 18 November 2015
Welcome toIntegrated Bioinformatics
Metabolic Modeling
I'm confused about whether glycolysis adds the H or removes it from NADH+
What Drives Glycolysis?
C Oe- pair
What Drives Glycolysis?
C Oe- pair
What Drives Glycolysis?
C Oe- pair
glucose
O
OH
HO
OH
OH OH O
OH
pyruvate
O
ATPO
OH
pyruvate
O
O
OHO
Gla3P
O
OHOO
ONAD+
NADH
O
OHOO
ADP
ATPGla 3-P
dehydrogenase
3-P-glycerate (3PG)
What Drives Glycolysis?
O
OHO
Gla3P
O
OHOO
ONAD+
NADH
O
OHOO
ADP
ATPGla 3-P
dehydrogenase
3-P-glycerate (3PG)
What Drives Glycolysis?
O
OHO
Gla3P
O
OHOO
ONAD+
NADH
O
OHOO
ADP
ATPGla 3-P
dehydrogenase
3-P-glycerate (3PG)
What Drives Glycolysis?
I'm confused about whether glycolysis adds the H or removes it from NADH+
O
OHO
Gla3P
O
OHOO
ONAD+
NADH
O
OHOO
ADP
ATPGla 3-P
dehydrogenase
3-P-glycerate (3PG)
What Drives Glycolysis?
My hunch was that reaction 12 is needed...
NADH
NAD+
O
O
OH
DHAP
O
OH
Glycerol-3P
OH
My hunch was that reaction 12 is needed...
since I'm not modeling Glo3p (since we don't care about any of the
steps that come after it) I need to leave out one of the Ks
Eisenthal & Cornish-Bowden (1998)O
O
OH
DHAP
O
OH
Glycerol-3P
OH
NADH
NAD+
My hunch was that reaction 12 is needed...
since I'm not modeling Glo3p (since we don't care about any of the
steps that come after it) I need to leave out one of the Ks...
Problem Set
0
1
2
3
4
5
6
1 200 399 598 797 996 1195 1394 1593 1792 1991 2190 2389 2588 2787 2986
Glcx
Glc
Glc6P
Fru6P
FruP2
Gla3P
DHAP
GbisP
3PG
PEP
Pyr
Pyrx
Pg
Pgc
NAD
NADH
Glo3P
Glo
How do you know when you’re done?
0
1
2
3
4
5
6
7
8
9
10
1 266 531 796 1061 1326 1591 1856 2121 2386 2651 2916
GlcxGlcGlc6PFru6PFruP2Gla3PDHAPGbisP3PGPEPPyrPyrxPg
0
1
2
3
4
5
6
1 200 399 598 797 996 1195 1394 1593 1792 1991 2190 2389 2588 2787 2986
Glcx
Glc
Glc6P
Fru6P
FruP2
Gla3P
DHAP
GbisP
3PG
PEP
Pyr
Pyrx
Pg
Pgc
NAD
NADH
Glo3P
Glo
How do you know when you’re done?
I think, therefore I am
Rene Descartes
0
1
2
3
4
5
6
1 200 399 598 797 996 1195 1394 1593 1792 1991 2190 2389 2588 2787 2986
Glcx
Glc
Glc6P
Fru6P
FruP2
Gla3P
DHAP
GbisP
3PG
PEP
Pyr
Pyrx
Pg
Pgc
NAD
NADH
Glo3P
Glo
How do you know when you’re done?
I am,therefore I’m at
steady state
Trypanosome
0
1
2
3
4
5
6
1 200 399 598 797 996 1195 1394 1593 1792 1991 2190 2389 2588 2787 2986
Glcx
Glc
Glc6P
Fru6P
FruP2
Gla3P
DHAP
GbisP
3PG
PEP
Pyr
Pyrx
Pg
Pgc
NAD
NADH
Glo3P
Glo
How do you know when you’re done?
0
1
2
3
4
5
6
7
8
9
10
1 266 531 796 1061 1326 1591 1856 2121 2386 2651 2916
GlcxGlcGlc6PFru6PFruP2Gla3PDHAPGbisP3PGPEPPyrPyrxPg
NewPrediction
external glucose
fructose bisphosphate
Metabolic modelHow to get there?
SQ4. Consider the metabolite fructose-bis- phosphate (FBP)... a. Identify where in glycolysis it appears.
0
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2
3
4
5
6
7
8
9
10
1 266 531 796 1061 1326 1591 1856 2121 2386 2651 2916
GlcxGlcGlc6PFru6PFruP2Gla3PDHAPGbisP3PGPEPPyrPyrxPg
NewPrediction
external glucose
fructose bisphosphate
Metabolic modelHow to get there?
?
SQ4b. Thinking of glycolysis as the flow of water through a hose with valves controlled by enzymes along the way, where is the obstruction...?
0
1
2
3
4
5
6
7
8
9
10
1 266 531 796 1061 1326 1591 1856 2121 2386 2651 2916
GlcxGlcGlc6PFru6PFruP2Gla3PDHAPGbisP3PGPEPPyrPyrxPg
NewPrediction
external glucose
fructose bisphosphate
Metabolic modelHow to get there?
?
SQ4c. If there is an obstruction at that point, what metabolite(s) would you expect to accumulate? What not?
0
1
2
3
4
5
6
7
8
9
10
1 266 531 796 1061 1326 1591 1856 2121 2386 2651 2916
GlcxGlcGlc6PFru6PFruP2Gla3PDHAPGbisP3PGPEPPyrPyrxPg
NewPrediction
external glucose
fructose bisphosphate
Metabolic model
?
What do you predict about other metabolites?
How to get there?
How to get there?
Investigate!
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