Single-cell metabolic models

For the quantitative description of the metabolic state of a cell, and likewise which is of particular interest within this review as input for metabolic models, experimental information about the level of metabolites is pivotal. Over the last decades, a variety of experimental methods for metabolite quantification have been developed, each with specific scopes and limits. While some methods aim at an exact quantification of single metabolites, other methods aim to capture relative levels of as many metabolites as possible. However, before providing an overview about the different methods for metabolite measurements, it is essential to recall that the time scales of metabolism are very fast Accordingly, for invasive methods samples have to be taken quickly and metabolism has to be stopped, usually by quick-freezing, for example, in liquid nitrogen. Subsequently, all further processing has to be performed in a way that prevents enzymatic reactions to proceed, either by separating enzymes and metabolites or by suspension in a nonpolar solvent. 

One of the pioneers of structured models in animal cell culture used a single-cell model (Batt and Kompala, 1989). Based on hybridoma metabolism (.Figure 8.6), the model was based on the formulation of four compartments amino acids (including the TCA precursors), the nucleotides (including DNA and RNA), the proteins, and lipids. The excreted byproducts (lactate and ammonia) and the excreted product (mAb) were also considered. However, although flexible for simulation of different... 

These advantages make single-cell models particularly well-suited to testing the plausibility of hypotheses about metabolic mechanisms. 

Single-Cell Metabolic Model Determination by Analysis of Microbial Populations... 

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