Presentation is loading. Please wait.

Presentation is loading. Please wait.

Welcome to Integrated Bioinformatics

Published byΉφαιστος Βαρουξής Modified over 5 years ago

Similar presentations

Presentation on theme: "Welcome to Integrated Bioinformatics"— Presentation transcript:

1 Welcome to Integrated Bioinformatics
Friday, 18 November 2011 Scenario 5 Metabolic Modeling The one and only concern I and most of my classmets have is the date of most modules needs to be updated in this website plus they need current informations. This is best viewed as a slide show. To view it, click Slide Show on the top tool bar, then View show. Click to start

2 New! Friday, 16 November 2012 What I learned from the questionnaires
The biological problem Overview of glycolysis Modeling a spontaneous reaction (ADP-As.pl) Vmax and Km Problem Set 5, #3 and maybe #11

3 How things work At the beginning of each module the general principle is discussed… After this, time is spent more on programming and how to biologically use it. Takes up majority of the time writing/modifying perl programs. Not much time analyzing the output or finding answers to biological questions.

4 About an hour of lecture, followed by an hour of coding.
How things work Lately we have been devoting the first hour to notes and defining a problem. The second hour is spent with Paul and Adam circulating to answer questions as the class works more or less independently. Usually, the first hour is devoted to lecture or going over the concepts of the module, and the next hour is spent working with Perl. About an hour of lecture, followed by an hour of coding.

5 I learn best by doing, not seeing nor hearing.
What things work Lectures so far have been a big part of it. The lectures help me greatly with understanding more of the complex concepts. Sitting and trying to figure out how to solve a problem helps me learn about it more. I learn best by doing, not seeing nor hearing.

6 What things work I am very weak when it comes to math.
I have no formal training in differential equations, but I've been able to work my through some biological scenarios that used them. I didn't understand the math,... I am very weak when it comes to math. I learn best by doing, not seeing nor hearing.

7 Trypanosoma brucei Causative agent of sleeping sickness
Life Cycle Central Nervous System Death

8 Trypanosoma brucei How to stop it?
Standard antibiotic targets Cell wall e.g. penicillins Bacterial ribosomes e.g. neomycin Bacterial RNA polymerase e.g. rifampicin Bacterial DNA gyrase e.g. nalidixic acid Trypanosomes have eukaryotic machinery, like us

9 Trypanosoma brucei How to stop it?
Them Glucose Us ATP Glycolysis Pyruvate Glycolysis ATP Pyruvate Citric Acid Cycle ATP

10 Trypanosoma brucei How to stop it?
Them Glucose Us Glycolysis Pyruvate ATP Glycolysis Pyruvate ATP Citric Acid Cycle ATP

11 Alternative to exhaustive lab testing
Glucose Glucose-6-P + ATP ADP Hexokinase Symbolically inhibitor1 dG6P/dt = kf [Glc][ATP] Mathematically $dG6P_dt = $kf*$glc*$atp Computationally … exhaustive computational modeling

12 Glycolysis dG6P/dt = +kf2 [Glc][ATP] kf3[G6P] dFDP/dt = +kf4 [F6P][ATP]-kf5[FDP] dGlc/dt = +kf1 [Glcx] -kr2[Glc] kf2[Glc][ATP] dF6P/dt = +kf3 [G6P]-kr3[F6P] kf4[F6P][AT] dDHAP/dt = +kf5 [FDP]+kr6[G3P] -kf6[DHAP] dG3P/dt = +kf5 [FDP]+kf6[DHAP] -kr6[G3P] kf7[G3P][NAD]+kry[13PGA][NADH] d13PGA/dt = kf7[G3P][NAD]-kry[13PGA][NADH] kf8[13PGA][ADP]+kr8[3PGA][ATP] . . . This is a very detailed modeling of glycolysis. It seems not feasible to model the enzyme kinetics when dealing large system of metabolic model.

13 Modeling Glycolysis I have studied it in a number of classes I learned about the glycolytic pathway in the past Need a little review, but comfortable with the basics. I understand the concept but I am definitely not an expert at it. Glucose->->->Pyruvate ===free energy

14 Modeling Glycolysis

15 electronegativity O > C > H
What is glycolysis glucose O OH HO blood cell Oxidation state OH O < electronegativity O > C > H O OH 2 pyruvate 2 ATP +

16 What is glycolysis glucose O OH HO permease blood cell O OH 2 pyruvate

17 What is glycolysis glucose O OH HO permease blood cell O OH 2 pyruvate

18 Anhydride (acid + acid)
What is glycolysis glucose O OH HO permease ATP O O-P-O -Adenosine blood cell Anhydride (acid + acid) O OH 2 pyruvate

19 Anhydride (acid + acid)
What is glycolysis glucose O OH HO permease ATP O O-P-O -Adenosine blood cell Anhydride (acid + acid) O OH 2 pyruvate

20 Anhydride (acid + acid)
What is glycolysis O O-P-O glucose O OH permease ADP O O-P-O O O-P-O blood cell -Adenosine Anhydride (acid + acid) O OH 2 pyruvate

21 Anhydride (acid + acid)
What is glycolysis glucose O OH permease ADP O O-P-O O O-P-O blood cell -Adenosine Anhydride (acid + acid) O OH 2 pyruvate

22 What is glycolysis ??? 2 2 ATP + glucose glucose-6P Ketone or aldehyde
ATP ADP glucose O OH HO glucose-6P O OH Ketone or aldehyde O Hexokinase ??? O Enol O OH 2 pyruvate 2 ATP +

23 What is glycolysis ??? 2 2 ATP + glucose glucose-6P Hexokinase
ATP ADP glucose O OH HO glucose-6P O OH O OH Hexokinase ??? O OH 2 pyruvate 2 ATP +

24 What is glycolysis 2 2 ATP + glucose glucose-6P fructose-6P
ATP ADP glucose O OH HO glucose-6P fructose-6P O OH O OH O OH Hexose-P isomerase Hexokinase O OH 2 pyruvate 2 ATP +

25 What is glycolysis 2 2 ATP + glucose glucose-6P fructose-6P
ATP ADP ATP ADP glucose O OH HO glucose-6P fructose-6P fructose-1,6 diP O OH O OH O OH Hexose-P isomerase Phospho fructokinase Hexokinase O OH 2 pyruvate 2 ATP +

26 What is glycolysis 2 2 ATP + glucose glucose-6P fructose-6P
ATP ADP ATP ADP glucose O OH HO glucose-6P fructose-6P fructose-1,6 diP O OH O OH O OH Hexose-P isomerase Phospho fructokinase Hexokinase Aldolase O O OH OH O O glyceraldehyde 3-P (Gla3P) Dihydroxy acetone P (DHAP) O OH 2 pyruvate 2 ATP +

27 What is glycolysis 2 2 ATP + glucose glucose-6P fructose-6P
ATP ADP ATP ADP glucose O OH HO glucose-6P fructose-6P fructose-1,6 diP O OH O OH O OH Hexose-P isomerase Phospho fructokinase Hexokinase Aldolase O Triose P isomerase O OH OH O O Gla3P DHAP O OH 2 pyruvate 2 ATP +

28 What is glycolysis 2 2 ATP + glucose glucose-6P fructose-6P
ATP ADP ATP ADP glucose O OH HO glucose-6P fructose-6P fructose-1,6 diP O OH O OH O OH Hexose-P isomerase Phospho fructokinase Hexokinase Aldolase O Triose P isomerase O OH OH O O Gla3P DHAP NAD+ O O OH NADH ADP ATP O OH 2 pyruvate Gla 3-P dehydrogenase 2 ATP + O OH 3-P-glycerate (3PG)

29 What is glycolysis 2 2 ATP + glucose glucose-6P fructose-6P
ATP ADP ATP ADP glucose O OH HO glucose-6P fructose-6P fructose-1,6 diP Ketone or aldehyde O Enol O OH O OH O OH Hexose-P isomerase Phospho fructokinase Hexokinase pyruvate Aldolase O O O 2 Triose P isomerase 2 ATP + O OH OH OH O O Gla3P DHAP NAD+ O O OH NADH ADP ATP Gla 3-P dehydrogenase 2-P-glycerate (3PG) O OH O OH P-Gla mutase 3-P-glycerate (3PG)

30 What is glycolysis 2 2 ATP + glucose glucose-6P fructose-6P
ATP ADP ATP ADP glucose O OH HO glucose-6P fructose-6P fructose-1,6 diP Ketone or aldehyde O Enol O OH O OH O OH Hexose-P isomerase Phospho fructokinase Hexokinase pyruvate Aldolase O O O 2 Triose P isomerase 2 ATP + O OH OH OH O O Gla3P DHAP Pyr Kinase NAD+ O O O OH NADH ADP ATP Enolase Gla 3-P dehydrogenase H2O OH O O OH H O P-Gla mutase O 2-P-glycerate (3PG) 3-P-glycerate (3PG)

31 Why is glycolysis 2 2 ATP + glucose glucose-6P fructose-6P
ATP ADP ATP ADP glucose O OH HO glucose-6P fructose-6P fructose-1,6 diP O OH O OH O OH Hexose-P isomerase Phospho fructokinase Hexokinase pyruvate Aldolase O O O 2 Triose P isomerase 2 ATP + O OH OH OH O O Gla3P DHAP Pyr Kinase NAD+ O O O OH NADH ADP ATP Enolase Gla 3-P dehydrogenase H2O O OH OH O H O P-Gla mutase O 2-P-glycerate (3PG) 3-P-glycerate (3PG)

32 Why is glycolysis 2 2 ATP + glucose glucose-6P fructose-6P
ATP ADP ATP ADP glucose O OH HO glucose-6P fructose-6P fructose-1,6 diP O OH O OH O OH Hexose-P isomerase Phospho fructokinase Hexokinase pyruvate Aldolase O O O 2 Triose P isomerase 2 ATP + O OH OH OH O O Gla3P DHAP Pyr Kinase NAD+ O O O OH NADH ADP ATP Enolase Gla 3-P dehydrogenase H2O O OH OH O H O P-Gla mutase O 2-P-glycerate (3PG) 3-P-glycerate (3PG)

33 Trypanosoma brucei How to exploit dependence on glycolysis?
Treatment blood cell Arsenate (AsO4 = Asi) Competitive with Pi

34 Trypanosoma brucei How to exploit dependence on glycolysis?
O-P-O O OH O O-P-O-CH2—CH—C Glyceraldehyde-3-P H O NAD+ NADH O-P-O-CH2—CH—C- O O-P-O OH ADP ATP O-P-O-CH2—CH—C-O O 3-P-Glycerate OH

35 Trypanosoma brucei How to exploit dependence on glycolysis?
OH O O-As-O O-P-O-CH2—CH—C Glyceraldehyde-3-P O H O NAD+ NADH H2O O-P-O-CH2—CH—C- O O-As-O OH ADP ATP O-P-O-CH2—CH—C-O O 3-P-Glycerate OH O O-As-O +

36 How to model this reaction?

37 How to model this reaction?

38 Characteristics of enzymes Chemical reactions
AMP-P-As AMP-P +Asi [AMP-P-As] k rate constant = d[AMP-P ] / dt concentration rate of change = = d[Asi] / dt rate of change = – = d[AMP-P-Asi] / dt rate of change

39 Characteristics of enzymes Chemical reactions
AMP-P-As AMP-P +Asi [AMP-P-As] k rate constant = – = d[AMP-P-Asi] / dt rate of change concentration [S] k = – = d[S] / dt A differential equation

40 Characteristics of enzymes Chemical reactions
AMP-P-As AMP-P +Asi [AMP-P-As] k rate constant = – = d[AMP-P-Asi] / dt rate of change concentration A differential equation = d[S] / dt = –k[S] = [S] Its solution?

41 Characteristics of enzymes Chemical reactions
AMP-P-As AMP-P +Asi [AMP-P-As] k rate constant = – = d[AMP-P-Asi] / dt rate of change concentration A differential equation = d[S] / dt = –k[S] = S0 e -k(t-to) [S] Its solution? = d[S] / dt Check: = S0 (–k) e -k(t-to) = -k S0 e -k(t-to) = -k [S]

42 Characteristics of enzymes Chemical reactions
Write an equation for the rate of increase of a rabbit population over time. (ignore all environmental effects) [R] = R0 2t/D A differential equation = d[S] / dt = –k[S] = S0 e -k(t-to) [S] Its solution? = d[S] / dt Check: = S0 (–k) e -k(t-to) = -k S0 e -k(t-to) = -k [S]

43 Characteristics of enzymes Chemical reactions
AMP-P-As AMP-P +Asi [AMP-P-As] k rate constant = – = d[AMP-P-Asi] / dt rate of change concentration A differential equation = d[S] / dt = –k[S] = S0 e -k(t-to) [S] Its solution? = d[S] / dt Check: = S0 (–k) e -k(t-to) = -k S0 e -k(t-to) = -k [S]

44 Characteristics of enzymes Chemical reactions
= S0 e -k(t-to) = d[S] / dt = –k[S]

45 Characteristics of enzymes Chemical reactions

46 Characteristics of enzymes Chemical reactions
= S0 e -k(t-to) S0 Δt

47 Characteristics of enzymes Chemical reactions
+ Δt d[S] / dt [S] = S0 S0 = d[S] / dt = –k[S] Δt

48 Characteristics of enzymes Chemical reactions
SQ1. Let’s try it. Link to ADP-As.pl Upload and plot results in Excel. For comparison, calculate on the same graph the analytical solution, using constants provided in ADP-As.pl

49 Characteristics of enzymes Chemical reactions
= S0 e -k(t-to) = d[S] / dt = –k[S]

50 Characteristics of enzymes Chemical reactions

51 Characteristics of enzymes Chemical reactions
= d[S] / dt = –k[S] [S] = S0 + Δt d[S] / dt Slope0 = -k[S0] [S1] = + Δt d[S] / dt S0 Slope1 = -k[S1] S0 Use average of Slope0 and Slope1 Δt

52 Characteristics of enzymes Chemical reactions
= d[S] / dt = –k[S] [S] = S0 + Δt d[S] / dt Slope0 = -k[S0] [S1] = S0 + Δt d[S] / dt Slope1 = -k[S1] S0 Use average of Slope0 and Slope1 Runge-Kutta method Δt

53 Characteristics of enzymes Enzymatic reactions
inhibitor1

54 Characteristics of enzymes Enzymatic reactions
What is the rate equation? Glucose-6-phosphate Fructose-6-phosphate ??? [G6P] k rate constant = = d[F6P] / dt rate of change concentration k ~ 0

55 Characteristics of enzymes Enzymatic reactions

56 Characteristics of enzymes Enzymatic reactions
E-complex G6P + E G6P·E F6P·E F6P + E [S] VMax [S] + Km v (velocity) = d[product] / dt = [product] = S0 + Δt d[S] / dt

57 Characteristics of enzymes Enzymatic reactions
velocity [S] [S] VMax [S] + Km v (velocity) = d[product] / dt =

58 Modeling systems of metabolic reactions Spontaneous vs Enzyme-catalyzed
Spontaneous reaction v = k [AMP~P~As] product [S]

59

60

Download ppt "Welcome to Integrated Bioinformatics"

Similar presentations

CARBOHYDRATE METABOLISM

CARBOHYDRATE METABOLISM
Scenario 5 Friday, 18 November 2011 Welcome to Integrated Bioinformatics Metabolic Modeling Click to start This is best viewed as a slide show. To view.

Scenario 5 Friday, 18 November 2011 Welcome to Integrated Bioinformatics Metabolic Modeling Click to start This is best viewed as a slide show. To view.
Chemistry of Glycolysis

Chemistry of Glycolysis
The first step of cellular respiration. What the is Glycolysis? The word glycolysis is constructed from glycose, an older term for glucose,

The first step of cellular respiration. What the is Glycolysis? The word glycolysis is constructed from glycose, an older term for glucose,
Overview of catabolic pathways

Overview of catabolic pathways
Principles of BIOCHEMISTRY Third Edition

Principles of BIOCHEMISTRY Third Edition
CHAPTER 14 Glucose Utilization and Biosynthesis –Harnessing energy from glucose via glycolysis –Fermentation under anaerobic conditions –Synthesis of glucose.

CHAPTER 14 Glucose Utilization and Biosynthesis –Harnessing energy from glucose via glycolysis –Fermentation under anaerobic conditions –Synthesis of glucose.
Chapter 14.1 and 14.2: Glycolysis and Feeder Pathways

Chapter 14.1 and 14.2: Glycolysis and Feeder Pathways
Fig 10.5 Overview of catabolic pathways Prentice Hall c2002 Chapter 11.

Fig 10.5 Overview of catabolic pathways Prentice Hall c2002 Chapter 11.
Enzyme Nomanclature.

Enzyme Nomanclature.
Cell Metabolism Things to look for in the metabolic process: 1. Energy transformations Examples: Kinetic energyworkPotential energy.

Cell Metabolism Things to look for in the metabolic process: 1. Energy transformations Examples: Kinetic energyworkPotential energy.
Prentice Hall c2002Chapter 111 Chapter 11 Glycolysis & Chapter 12 Citric Acid Cycle Lectures 19: Glycolysis (I) October 17, 2003 Haining Zhu Dept. of Molecular.

Prentice Hall c2002Chapter 111 Chapter 11 Glycolysis & Chapter 12 Citric Acid Cycle Lectures 19: Glycolysis (I) October 17, 2003 Haining Zhu Dept. of Molecular.
Protein Structure, Function and The Enzymes of Glycolysis

Protein Structure, Function and The Enzymes of Glycolysis
1 SURVEY OF BIOCHEMISTRY Glycolysis. 2 Glycolysis Overview Glycolysis: breakdown of glucose into pyruvate with net production of ATP Occurs in cytosol.

1 SURVEY OF BIOCHEMISTRY Glycolysis. 2 Glycolysis Overview Glycolysis: breakdown of glucose into pyruvate with net production of ATP Occurs in cytosol.
GLYCOLYSIS Glucose ATP Hexokinase ADP Glucose 6-phosphate

GLYCOLYSIS Glucose ATP Hexokinase ADP Glucose 6-phosphate
Announcements Reading for today on glycolysis: pp. 221-234 Homework due today: Problems 8-5, 8-7 –In both problems, use the favorable free energy change.

Announcements Reading for today on glycolysis: pp Homework due today: Problems 8-5, 8-7 –In both problems, use the favorable free energy change.
Glycolysis Overview of cellular respiration 4 metabolic stages –Anaerobic respiration 1. Glycolysis –respiration without O 2 –in cytosol –Aerobic respiration.

Glycolysis Overview of cellular respiration 4 metabolic stages –Anaerobic respiration 1. Glycolysis –respiration without O 2 –in cytosol –Aerobic respiration.
CHAPTER 16 Glycolysis.

CHAPTER 16 Glycolysis.
Regulation of Glycoysis. Pyruvate can go in three major directions after glycolysis Under aerobic conditions pyruvate is oxidized to Acetyl-CoA which.

Regulation of Glycoysis. Pyruvate can go in three major directions after glycolysis Under aerobic conditions pyruvate is oxidized to Acetyl-CoA which.
You design lecture a.Discuss the research that “proved” Rotational Catalysis b.Review Metabolism and Electron Transport Chain from previous two classes.

You design lecture a.Discuss the research that “proved” Rotational Catalysis b.Review Metabolism and Electron Transport Chain from previous two classes.

Similar presentations

Ads by Google