Trends in Biochemical Sciences
ForumMetabolic databases – what next?
Section snippets
Metabolic databases in the year 2000
There are many variations on the theme of the on-line metabolic database (Box 1). Some sites contain information that is based on the biochemistry of a single organism. For example, the EcoCyc database claims to contain a complete description of Escherichia coli metabolism. Others, such as ENZYME, contain a more general set of information. There has been a tendency for larger metabolic databases to be regarded automatically as significant new research tools to overcome limitations of empirical
The current model – strengths and limitations
The usefulness of the metabolic map as a two-dimensional representation of the chemistry of the cell is limited by its own complexity. In a historical context, the focus on metabolites is entirely understandable, as most new metabolites were characterized well before the molecules that catalysed their interconversion. However, the complex divergence, convergence and interconnections of all known pathways in a cell means that representation in two dimensions now requires considerable distortion.
Metabolic pathway analysis
Metabolic databases are largely repositories of information and their research value depends on appropriate data handling. Thus, such database availability has led to an increasing interest in metabolic analysis. However, as pointed out by Stephanopoulos 4, ‘in contrast to the tremendous progress in elucidating the properties of single enzymes at the protein and gene level, relatively little has been accomplished in understanding the properties of metabolic and information pathways, their
A new approach to metabolic analysis?
Because cybernetics derives from systems thinking, ways in which more general systems concepts might be applied to metabolic analysis are being explored. In other fields, systems analysis has developed to facilitate the study of any aspect of a complex, self-organized system. The metabolic map provides an excellent example of such a system. This has been recognized both implicitly, for example in the dot-and-line representations of metabolism by Alberts 14, and explicitly by systems theorists 3.
New approaches, new questions
The systems perspective leads to two conclusions. First, databases must be extended to enable a user to query the role of either metabolites or enzymes (as in Fig. 1 and 2), or other information. For example, species of similar Gibbs free energy could be clustered together, in order to pose questions pertaining to cellular thermodynamics. Second, the form of the table or network, and the precise mode of analysis, will be dictated by the particular questions we want to ask, whether these be
Concluding remarks
Biochemistry needs to acclimatize in the era of bioinformatics. Metabolic databases are beginning to provide a complete qualitative description of the cell. They arose in order to store and analyse the seemingly unmanageable weight of information, but have yet to challenge the basic paradigm in which metabolism was conceived. Here the authors propose a new approach, changing the dimensions of the traditional metabolic map to permit an alternative focus on the macromolecular machinery of the
Acknowledgements
This work was supported in part by a University of Canterbury Scholarship to J.A.W. J.A.G. would like to thank Prof. Janos Hajdu, University of Uppsala, for stimulating discussions.
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