Systems Biology: Simulation of Dynamic Network States

Contents......Page 8
Preface......Page 12
1.1 Biological networks......Page 16
1.2 Why build and study models?......Page 20
1.3 Characterizing dynamic states......Page 21
1.4 Formulating dynamic network models......Page 22
1.5 The basic information is in a matrix format......Page 26
1.6 Studying dynamic models......Page 28
1.7 Summary......Page 31
2.1 Properties of dynamic states......Page 32
2.2 Primer on rate laws......Page 35
2.3 More on aggregate variables......Page 40
2.4 Time-scale decomposition......Page 43
2.5 Network structure versus dynamics......Page 46
2.6 Physico-chemical effects......Page 49
2.7 Summary......Page 51
Part I Simulation of dynamic states......Page 54
3.1 Numerical solutions......Page 56
3.2 Graphically displaying the solution......Page 58
3.3 Post-processing the solution......Page 64
3.4 Demonstration of the simulation procedure......Page 66
3.5 Summary......Page 71
4.1 Basic properties of reactions......Page 73
4.2 The reversible linear reaction......Page 75
4.3 The reversible bilinear reaction......Page 77
4.4 Connected reversible linear reactions......Page 81
4.5 Connected reversible bilinear reactions......Page 85
4.6 Summary......Page 90
5.1 Enzyme catalysis......Page 91
5.2 Deriving enzymatic rate laws......Page 93
5.3 Michaelis–Menten kinetics......Page 95
5.4 Hill kinetics for enzyme regulation......Page 100
5.5 The symmetry model......Page 105
5.6 Scaling dynamic descriptions......Page 109
5.7 Summary......Page 111
6.1 Basic concepts......Page 112
6.2 Reversible reaction in an open environment......Page 115
6.3 Michaelis–Menten kinetics in an open environment......Page 119
6.4 Summary......Page 122
Part II Biological characteristics......Page 124
7.1 Cellular composition and ultra-structure......Page 126
7.2.1 What are typical concentrations?......Page 131
7.2.2 What are typical metabolic fluxes?......Page 132
7.2.3 What are typical turnover times?......Page 136
7.2.4 What are typical power densities?......Page 138
7.3.2 What are typical protein concentrations?......Page 139
7.3.3 What are typical fluxes?......Page 141
7.3.4 What are typical turnover times?......Page 142
7.4.1 What are typical cell-specific production rates?......Page 143
7.4.2 Balancing the fluxes and composition in an entire cell......Page 144
7.5 Summary......Page 146
8.1 Bilinear biochemical reactions......Page 147
8.2 Bilinearity leads to a tangle of cycles......Page 149
8.3.1 The basic structure of the \"core\'\' module......Page 152
8.3.2 Buffering the energy charge......Page 155
8.3.3 Open system: long-term adjustment of the capacity......Page 158
8.4 Charging and recovering high-energy bonds......Page 160
8.5 Summary......Page 164
9.1 Regulation of enzymes......Page 165
9.2 Regulatory signals: phenomenology......Page 167
9.3 The effects of regulation on dynamic states......Page 168
9.4 Local regulation with Hill kinetics......Page 171
9.4.1 Inhibition......Page 172
9.4.2 Activation......Page 173
9.5 Feedback inhibition of pathways......Page 176
9.6.1 Regulation of protein synthesis......Page 180
9.6.2 Tight regulation of enzyme activity......Page 182
9.7 Summary......Page 184
Part III Metabolism......Page 186
10.1 Glycolysis as a system......Page 188
10.2 The stoichiometric matrix......Page 190
10.3 Defining the steady state......Page 196
10.4 Simulating mass balances: biochemistry......Page 200
10.5 Pooling: towards systems biology......Page 204
10.6 Ratios: towards physiology......Page 214
10.7 Assumptions......Page 217
10.8 Summary......Page 218
11.1 The pentose pathway......Page 219
11.2 The combined stoichiometric matrix......Page 225
11.3 Defining the steady state......Page 229
11.4 Simulating the dynamic mass balances......Page 231
11.5 Pooling: towards systems biology......Page 233
11.6 Ratios: towards physiology......Page 234
11.7 Summary......Page 237
12.1 AMP metabolism......Page 239
12.2 Network integration......Page 246
12.3 Whole-cell models......Page 255
12.4 Summary......Page 256
Part IV Macromolecules......Page 258
13.1 Hemoglobin: the carrier of oxygen......Page 260
13.2 Describing the states of hemoglobin......Page 263
13.3 Integration with glycolysis......Page 268
13.4 Summary......Page 272
14.1 Phosphofructokinase......Page 274
14.2 The steady state......Page 280
14.3 Integration of PFK with glycolysis......Page 284
14.4 Summary......Page 289
15.1 Building dynamic models in the omics era......Page 290
15.2 Going forward......Page 295
 Appendix A Nomenclature......Page 300
B.3 Dynamic simulation: the basic procedure......Page 303
B.4 Chemical reactions......Page 304
B.5 Enzyme kinetics......Page 307
B.6 Open systems......Page 310
B.7 Orders of magnitude......Page 311
B.8 Stoichiometric structure......Page 313
B.9 Regulation as elementary phenomena......Page 314
B.11 Coupling pathways......Page 317
B.12 Forming integrated networks......Page 318
B.13 Hemoglobin......Page 319
B.14 Regulated enzymes......Page 320
References......Page 321
Index......Page 329