Monday, 19 November 2012

# Monday, 19 November 2012

## Monday, 19 November 2012

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##### Presentation Transcript

1. Monday, 19 November 2012 • Overview of modeling strategy • Determining rates of changes of metabolites (Problem 3) • Overview of Eisenthal & Cornish-Bowden • Modeling the hexokinase reaction • Modification of Glycolysis.pl

2. Should we meet Wednesday? Just another day... Rather not... I will also be here, willing and able. I would personally prefer no class, however if majority of the class is willing to have class that day I am fine with that too. I Am fine either way Maybe something special... Wednesday could be a review/question day. .. I need to drive to PA and cook for 12 people. The more time I have for this, the better. I would prefer not having class. ...Wednesday might be a good day for students to get one-on-one explanations of the material. Conditional on... ...if you think we (as a class) are ahead or understanding what we should, well enough to take a test over it, then not meeting Wednesday is fine. However, if you think we are struggling and/or too far behind and need to catch up, in order to do well on the test, then we should maybe meet ..

3. Should we meet Wednesday? Where are we going?

4. The Goal Trypanosomes

5. The Goal Model of glycolysis G6P ...

6. The Goal Model of glycolysis d(G6P)/dt = k3[glucose][ATP] d(F6P)/dt = k4[G6P] d(FDP)/dt = k6[F6P][ATP] G6P ... d(pyruvate)/dt = k20[PEP][ADP]

7. G6P 0 Time The Goal Model of glycolysis d(G6P)/dt = k3[glucose][ATP] d(F6P)/dt = k4[G6P] d(FDP)/dt = k6[F6P][ATP] ... d(pyruvate)/dt = k20[PEP][ADP] Set-starting-concentrations FUNCTION Set-starting-concentrations ASSIGN glucose10ASSIGN G6P3ASSIGN ATP2ASSIGN . . . How?

8. G6P 0 Time The Goal Model of glycolysis d(G6P)/dt = k3[glucose][ATP] d(F6P)/dt = k4[G6P] d(FDP)/dt = k6[F6P][ATP] ... d(pyruvate)/dt = k20[PEP][ADP] Set-starting-concentrations FUNCTION Set-starting-concentrations ASSIGN glucose10ASSIGN G6P3ASSIGN ATP2ASSIGN . . . Where to get the numbers?

9. G6P 0 Time The Goal Model of glycolysis d(G6P)/dt = k3[glucose][ATP] d(F6P)/dt = k4[G6P] d(FDP)/dt = k6[F6P][ATP] ... dt d(pyruvate)/dt = k20[PEP][ADP] Set-starting-concentrations CONSIDER EACHtFROMdtTOtMaxBY dt How small dt?

10. dG6P G6P 0 Time The Goal Model of glycolysis d(G6P)/dt = k3[glucose][ATP] d(F6P)/dt = k4[G6P] d(FDP)/dt = k6[F6P][ATP] ... d(pyruvate)/dt = k20[PEP][ADP] Set-starting-concentrations CONSIDER EACHtFROMdtTOtMaxBY dt Calculate-rates-of-changes-in-concentrations Calculate-changes-in-concentrations Add-changes-to-old-concentrations How?

11. dG6P G6P 0 Time The Goal Model of glycolysis d(G6P)/dt = k3[glucose][ATP] d(F6P)/dt = k4[G6P] d(FDP)/dt = k6[F6P][ATP] ... d(pyruvate)/dt = k20[PEP][ADP] Set-starting-concentrations CONSIDER EACHtFROMdtTOtMaxBY dt Calculate-rates-of-changes-in-concentrations FUNCTION Calculate-rates-of-changes-in-concentrations ASSIGN dG6P_dt = k3 * glucose * ATPASSIGN dF6P_dt = k4 * G6PASSIGN . . . Where to get values for k?

12. dG6P G6P 0 Time ASSIGN G6P = dG6P_dt * intervalASSIGN F6P = dF6P_dt * intervalASSIGN . . . The Goal Model of glycolysis d(G6P)/dt = k3[glucose][ATP] d(F6P)/dt = k4[G6P] d(FDP)/dt = k6[F6P][ATP] ... d(pyruvate)/dt = k20[PEP][ADP] Set-starting-concentrations CONSIDER EACHtFROMdtTOtMaxBY dt Calculate-rates-of-changes-in-concentrations Calculate-changes-in-concentrations FUNCTION Calculate-changes-in-concentrations Change = rate * time

13. dG6P G6P 0 Time The Goal Model of glycolysis d(G6P)/dt = k3[glucose][ATP] d(F6P)/dt = k4[G6P] d(FDP)/dt = k6[F6P][ATP] ... d(pyruvate)/dt = k20[PEP][ADP] Set-starting-concentrations CONSIDER EACHtFROMdtTOtMaxBY dt Calculate-rates-of-changes-in-concentrations Calculate-changes-in-concentrations Add-changes-to-old-concentrations

14. dG6P G6P 0 Time ASSIGN G6P = G6P + G6PASSIGN F6P = F6P + F6PASSIGN . . . The Goal Model of glycolysis d(G6P)/dt = k3[glucose][ATP] d(F6P)/dt = k4[G6P] d(FDP)/dt = k6[F6P][ATP] ... d(pyruvate)/dt = k20[PEP][ADP] Set-starting-concentrations CONSIDER EACHtFROMdtTOtMaxBY dt Calculate-rates-of-changes-in-concentrations Calculate-changes-in-concentrations Add-changes-to-old-concentrations FUNCTION Add-changes-to-old-concentrations New = old + change

15. dG6P G6P 0 Time The Goal Model of glycolysis d(G6P)/dt = k3[glucose][ATP] d(F6P)/dt = k4[G6P] d(FDP)/dt = k6[F6P][ATP] ... d(pyruvate)/dt = k20[PEP][ADP] Set-starting-concentrations CONSIDER EACHtFROMdtTOtMaxBY dt Calculate-rates-of-changes-in-concentrations Calculate-changes-in-concentrations Add-changes-to-old-concentrations

16. G6P 0 Time The Goal Model of glycolysis d(G6P)/dt = k3[glucose][ATP] d(F6P)/dt = k4[G6P] d(FDP)/dt = k6[F6P][ATP] ... d(pyruvate)/dt = k20[PEP][ADP] Set-starting-concentrations CONSIDER EACHtFROMdtTOtMaxBY dt Calculate-rates-of-changes-in-concentrations Calculate-changes-in-concentrations Add-changes-to-old-concentrations

17. G6P 0 Time The Goal Model of glycolysis d(G6P)/dt = k3[glucose][ATP] d(F6P)/dt = k4[G6P] d(FDP)/dt = k6[F6P][ATP] ... d(pyruvate)/dt = k20[PEP][ADP] Set-starting-concentrations CONSIDER EACHtFROMdtTOtMaxBY dt Calculate-rates-of-changes-in-concentrations Calculate-changes-in-concentrations Add-changes-to-old-concentrations

18. G6P 0 Time The Goal Model of glycolysis d(G6P)/dt = k3[glucose][ATP] d(F6P)/dt = k4[G6P] d(FDP)/dt = k6[F6P][ATP] ... d(pyruvate)/dt = k20[PEP][ADP] Set-starting-concentrations CONSIDER EACHtFROMdtTOtMaxBY dt Calculate-rates-of-changes-in-concentrations Calculate-changes-in-concentrations Add-changes-to-old-concentrations How to program this?

19. Set-starting-concentrations CONSIDER EACHtFROMdtTOtMaxBY dt Calculate-rates-of-changes-in-concentrations Calculate-changes-in-concentrations Add-changes-to-old-concentrations

20. Set-starting-concentrations CONSIDER EACHtFROMdtTOtMaxBY dt Calculate-rates-of-changes-in-concentrations Calculate-changes-in-concentrations Add-changes-to-old-concentrations

21. Should we meet Wednesday? Just another day... Rather not... I will also be here, willing and able. I would personally prefer no class, however if majority of the class is willing to have class that day I am fine with that too. I Am fine either way Maybe something special... Wednesday could be a review/question day. .. I need to drive to PA and cook for 12 people. The more time I have for this, the better. I would prefer not having class. ...Wednesday might be a good day for students to get one-on-one explanations of the material. Conditional on... ...if you think we (as a class) are ahead or understanding what we should, well enough to take a test over it, then not meeting Wednesday is fine. However, if you think we are struggling and/or too far behind and need to catch up, in order to do well on the test, then we should maybe meet ..

22. Friday, 19 November 20120 • Overview of modeling strategy • Determining rates of changes of metabolites (Problem 3) • Overview of Eisenthal & Cornish-Bowden • Modeling the hexokinase reaction • Modification of Glycolysis.pl

23. Set-starting-concentrations CONSIDER EACHtFROMdtTOtMaxBY dt Calculate-rates-of-changes-in-concentrations Calculate-changes-in-concentrations Add-changes-to-old-concentrations

24. Rates of changes of metabolites

25. Rates of changes of metabolites k1 AMP-P-As AMP-P +Asi d[AMP-P ] / dt = k1 [AMP-P-As]

26. Rates of changes of metabolites k1 AMP-P-As AMP-P +Asi k2 d[AMP-P ] / dt = k1 [AMP-P-As] - k2 [AMP-P][Asi] Units of k1 and k2?

27. Rates of changes of metabolites

28. Friday, 19 November 20120 • Overview of modeling strategy • Determining rates of changes of metabolites (Problem 3) • Overview of Eisenthal & Cornish-Bowden • Modeling the hexokinase reaction • Modification of Glycolysis.pl

29. Overview of Eisenthal and Cornish-Bowdin

30. noncompetitive uncompetitive competitive

31. noncompetitive uncompetitive competitive

32. PEPc + ADPc Pyrc + ATPc

33. ? ? PEPc + ADPc Pyrc + ATPc 0 0

34. h h PEPc + ADPc Pyrc + ATPc 0 0

35. Overview of Eisenthal and Cornish-BowdinHow to go from article to program

36. Overview of Eisenthal and Cornish-BowdinHow to go from article to program

37. Friday, 19 November 20120 • Overview of modeling strategy • Determining rates of changes of metabolites (Problem 3) • Overview of Eisenthal & Cornish-Bowden • Modeling the hexokinase reaction • Modification of Glycolysis.pl

38. Modeling systems of metabolic reactions Glycolysis.pl Modeling of reactions of glycolysis Transform ADP-As.pl to Glycolysis.pl(just hexokinase reaction)

39. Friday, 19 November 20120 • Overview of modeling strategy • Determining rates of changes of metabolites (Problem 3) • Overview of Eisenthal & Cornish-Bowden • Modeling the hexokinase reaction • Modification of Glycolysis.pl

40. Modeling GlycolysisUsing data of Eisenthal & Cornish-Bowdin Glycolysis.pl Modeling of reactions of glycolysis

41. Modeling GlycolysisUsing data of Eisenthal & Cornish-Bowdin Glycolysis.pl Modeling of reactions of glycolysis