# Presentation: 489848

## Metabolic and Functional Reconstruction Of Cellular Networks

- Genome Sequence Analisis and Annotation

- Public Sequence Data Bases

- To Mathematical Analysis and Simulation of Reconstructed Networks

- New Sequenced Genome

- Experimental Knowledge Published in the Literature

- List of Genes and Their Asserted Functions

- Data Bases
- EMP
- MPW
- ERM

- Visualization

- Nomencatures of
- Genes
- Proteins
- Enzymes
- Complexes
- Intermediates, etc.

- Conversion Metabolic Reconstructions into Mathematical ModelsMathematical Analysis and Simulation of Reconstructed Networks

**Metabolic and Functional Reconstruction Of Cellular Networks**

- Reconstructed Metabolic Maps

## Slide 2

## Slide 3

##                                                                              Gene Category List 

- _[  ](http://www.kazusa.or.jp/cyanobase/)_                              _[  ](http://www.kazusa.or.jp/cyanobase/Synechocystis/)_                                           **Gene Category List**

- Steady State
- Flux Analysis

- Reconstructed Stoichiometric Network

- Mathematical Analysis and Simulation of Reconstructed Networks

- Steady State
- Kinetic Models

- Predicting  Non-Stoichiometric Regulatory Mechanisms and Parameter Values

- Dynamic Models of Cells and Their Populations

- Bifurcation analysis and Computational Experiments

- Fitting Dynamic Models to Experimental Data

- Experimental Data On Intracellular Dynamics

- Computing Drug Targets

- Metabolic Engineering

- Understanding Cellular Life Phenomena

- New Bio- Agro- or Medical Technologies

- Fitting and Optimizing the Models

- Experimental Data On Extracellular Fluxes

- Predicting Metabolic Phenotype

- Computing
- Intracellular Fluxes

## Slide 5

## Steady State Kinetic Analysis

**Predicts new phenomena and helps to design new experiments**
**Optimization of steady state kinetic models allows to predict regulatory mechanisms and their parameter values**
**Demonstrates that the essential parts of the cellular metabolism cannot function in a steady state**

## Beyond sequence analysis 

- GAP

- IMP

- AS

- AMP

- ADP

- ATP

- ADP

- ATP

- TP

- Pyruvate

- ADP

- ATP

- PRPP

- DHPP

- FBP

- F6P

- ATP

- ADP

- Pentose Phosphate Pathway

- ATP
- ADP
- IMP

**-**

**+**

**+**

**+**

**-**

**-**

**-**

**-**

**-**

- ATP
- AMP

**+**

**+**

**Beyond sequence analysis**
- Theoretically predicted allosteric regulatory mechanisms via optimization of a mathematical model derived from metabolic reconstruction

- Activation

- Activation

- Inhibition

## R

- FBP

- TCA

- TP

**Cyanophycin**

**Glycogen**

- HMP

- ADP

- ATP

- ATP

- ADP

- ATP

- ADP

- GTP

- GDP

- H20

- Pi

- Pi

**R**

**R**

**+**

**-**

**-**

- 2ATP

- 2ADP

**A number of reconstructed futile cycles must be controlled in time reciprocally to prevent theoretically inevitable energy collapse.**
- Such regulation results in anti-phase oscillations in glycogen and cyanophycin content

**Futile substrate cycling**

## Mathematical Simulation Predict Perfect Stabilization of ATP in Uncontrolled Cell Energy Metabolism

**There is no nonzero ****stationary ATP concentration beyond this activity**

## R

***Left*****: During the light phase glycogen (  ) goes up, oxygen evolution (not shown) is high, and N****2 ****fixation (  ) is shut down. ***** Right:  *****The same experiment under continuous light.***** *****The is a clear proof that the external light modulation is not the primary cause of the temporal organization. (From Schneegurt M.A., et al. *****J.Physiol*****., 33, 639-642)**** **

- FBP

- TCA

- TP

**Cyanophycin**

**Glycogen**

- HMP

- ADP

- ATP

- ATP

- ADP

- ATP

- ADP

- GTP

- GDP

- H20

- Pi

- Pi

**R**

**+**

**-**

**-**

- 2ATP

- 2ADP

## Non-Linear Biochemical OscillatorWith a Stabilizing Negative Feedback 

***A***

***B***

***E******B***

***S***

***P***

***Controller***

***E******B***

***S***

***Negative Feedback***

- Non-Linear Biochemical OscillatorWith a Stabilizing Negative Feedback

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| --- |

***V******s***

## Slide 12

## Slide 13