metabolicfluxanalysis代谢通量分析..doc

BIOE321Part III Pathway and Metabolic Engineering Metabolic Flux Analysis II.1 Introduction (Metabolic Engineering, Stephanopoulos et al) Metabolic flux analysis (MFA) is a powerful methodology for the determination f metabolic pathway fluxes. In this approach, the intracellular fluxes are calculated by using a stoichiometric model (metabolic pathway map) for the major intracellular reactions and applying mass balances around intracellular metabolites. A set of measured extracellular fluxes , typically uptake rates of substrates and secretion rates of metabolites, is used as input to the calculations. The result of flux calculation is a metabolic flux map showing a diagram of the biochemical reactions included in the calculations along with an estimate of the steady state rate (i.e., the flux) at which each reaction in the diagram occurs. II.2 Example (Metabolic Engineering, Stephanopoulos et al) II.3 Other Applications of MFA (Metabolic Engineering, Stephanopoulos et al) II.3 Concept of reaction stoichiometry Example 1 Consider a simple reaction network occurring in a constant volume cell shown in the following diagram in the above reaction network, S0 is changed into S (this may consider as the intake of substrate from outside of the cell), S is converted to A and B through reaction r1 and r2, A is converted to C by reaction r3, and B is converted to D through reaction r4. Notice that in general the reaction does not contain the stoichiometric information. It is usually accompanied by a set of biochemical reactions, whose stoichiometric relationships have already established. For example, Glucose + PEP - Glucose-6-P + pyruvate or pyruvate + NADH - lactate + NAD+ or Glucose-6-P + ATP - 2 Glyceraldehyde 3-P + ADP Referring back to our previous example, suppose the reaction network follows the following reactions Referring back to our current example, suppose the reaction network follows the following reactions Material Balance on the four species So, S, A,