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## Monday, 19 November 2012

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**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**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 ..**Should we meet Wednesday?**Where are we going?**The Goal**Trypanosomes**The Goal**Model of glycolysis G6P ...**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]**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?**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?**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?**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?**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?**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**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**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**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**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**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**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?**I was wondering if your updated PowerPoint would be posted**online**Set-starting-concentrations**CONSIDER EACHtFROMdtTOtMaxBY dt Calculate-rates-of-changes-in-concentrations Calculate-changes-in-concentrations Add-changes-to-old-concentrations**Set-starting-concentrations**CONSIDER EACHtFROMdtTOtMaxBY dt Calculate-rates-of-changes-in-concentrations Calculate-changes-in-concentrations Add-changes-to-old-concentrations**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 ..**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**Set-starting-concentrations**CONSIDER EACHtFROMdtTOtMaxBY dt Calculate-rates-of-changes-in-concentrations Calculate-changes-in-concentrations Add-changes-to-old-concentrations**Rates of changes of metabolites**k1 AMP-P-As AMP-P +Asi d[AMP-P ] / dt = k1 [AMP-P-As]**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?**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**noncompetitive**uncompetitive competitive**noncompetitive**uncompetitive competitive**?**? PEPc + ADPc Pyrc + ATPc 0 0**h**h PEPc + ADPc Pyrc + ATPc 0 0**Overview of Eisenthal and Cornish-BowdinHow to go from**article to program**Overview of Eisenthal and Cornish-BowdinHow to go from**article to program**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**Modeling systems of metabolic reactions**Glycolysis.pl Modeling of reactions of glycolysis Transform ADP-As.pl to Glycolysis.pl(just hexokinase reaction)**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**Modeling GlycolysisUsing data of Eisenthal & Cornish-Bowdin**Glycolysis.pl Modeling of reactions of glycolysis**Modeling GlycolysisUsing data of Eisenthal & Cornish-Bowdin**Glycolysis.pl Modeling of reactions of glycolysis