Metabolic balance sheets.

toichiometric analysis has the same function in biochemistry as book-keeping has in business. Both deal with the inputs and outputs in flow systems, and studying the stoichiometric structure of a metabolic network might seem only slightly more exciting than a visit to an accountant's office. Times change, however, and progress in systems biology will involve paying closer attention to stoichiometry than seemed necessary in the past. The benefits should be that, with minimal knowledge of kinetic parameters, we will be able to predict how systems will respond to changes in conditions , and how they can be genetically engineered to produce desirable characteristics. The growing knowledge of genomes of different organisms has brought new life to the study of metabolic networks, and a striking example appears on page 190 of this issue 1. Stelling and collaborators discuss there the idea that, by breaking a network down into 'elementary flux modes' , based on simple accounting for metabolic inputs and outputs, possible properties of the network can be predicted. A typical biological network such as the central metabolism of the gut bacterium Escherichia coli consists of many processes that operate simultaneously and in parallel. For example, many different metabolic products are being synthesized at different rates at the same time as substrates such as glucose are being consumed to supply power for all the activity. Even when all the individual processes have been identified, it is no trivial matter to predict how the properties of the network as a whole will change if the activity of one enzyme is changed. It used to be widely assumed, for example , that complete elimination of an enzyme activity would have obvious effects, but this expectation has been overthrown by observations of the effects of gene knockouts in various organisms: in E. coli, fewer than 300 out of 4,000 genes are 'essential' in the sense that deleting one of them prevents growth on a rich medium 2. Many of the others can be deleted (one at a time) without producing any evident consequences, even for growth on a medium containing restricted nutrients ; in other words, they are 'silent'. As well as discovering the functions of these silent genes, it is crucial to know why they are not essential, and elementary flux modes provide a tool for addressing this question. Consider, for example, the simple branched network of six reactions shown in Fig. 1a. …