IN-VIVO ANALYSIS OF METABOLIC DYNAMICS IN SACCHAROMYCES-CEREVISIAE .2. MATHEMATICAL-MODEL

A mathematical model of glycolysis in Saccharomyces cerevisiae is pres ented. The model is based on rate equations for the individual reactio ns and aims to predict changes in the levels of intra- and extracellul ar metabolites after a glucose pulse, as described in part I of this s tudy. Kinetic analysis focuses on a time scale of seconds, thereby neg lecting biosynthesis of new enzymes. The model structure and experimen tal observations are related to the aerobic growth of the yeast. The m odel is based on material balance equations of the key metabolites in the extracellular environment, the cytoplasm and the mitochondria, and includes mechanistically based, experimentally matched rate equations for the individual enzymes. The model includes removal of metabolites from glycolysis and TCC for biosynthesis, and also compartmentation a nd translocation of adenine nucleotides. The model was verified by in vivo diagnosis of intracellular enzymes, which includes the decomposit ion of the network of reactions to reduce the number of parameters to be estimated simultaneously. Additionally, sensitivity analysis guaran tees that only those parameters are estimated that contribute to syste ms trajectory with reasonable sensitivity. The model predictions and e xperimental observations ag ree reasonably well for most of the metabo lites, except for pyruvate and adenine nucleotides. (C) 1997 John Wile y & Sons. Inc.