Complexity

It is evident that in the operation of metabolic pathways, as in most complex systems, there are readily describable features or responses that are not inherent in the kinetic behavior of the individual enzymes, when they are studied in isolation. The responses of the system as a whole can manifest as unanticipated fluctuations in metabolite concentrations, including stable periodicities, growth in size of micro-, meso-, or even macroscopic structures, and possibly even self-replication of the system.

There are basically three patterns, or networks, of interconnection that operate within metabolic pathways in cells. The first is the interconnectedness that is represented by the chemical transformations that are predicated on the laws of chemical reactivity; the reactions involve substrates that become products, that in turn become substrates for other enzymes. The second entails reactants that activate or inhibit, and thus control, the enzymes of the pathway at places in the sequence that are often far removed, chemically, from the enzyme-catalyzed reactions that produce them. And the third level involves the relative abundance or amounts of individual enzymes that are determined by their rates of breakdown and rates of synthesis, via proteases and via mRNA, respectively. Preceding the translation of mRNA into protein is the regulation of transcription of DNA by transcription factors, many of which are hormone- and metabolite-binding proteins. Hormones and metabolites from outside a metabolic pathway therefore regulate it by bringing about changes in enzyme concentrations.

These three levels of interconnection are what shape the kinetic behavior of a metabolic pathway. The responses of the pathway to perturbations of enzyme activity, rates of substrate supply or product removal, do not succumb readily to intuitive analysis, at least not quantitative analysis; the systems are just too complex for that. The situation is akin to what Aristotle alluded to when considering certain features of geometrical systems: "The whole is greater than the sum of the parts." For metabolic pathways, the adage can be fruitfully reworded to: "The responses of the system are different from those predicted from the responses of the parts when they are studied alone." For example, individual enzymes in a closed system never display regular periodic variations in reactant concentrations, but sequences of enzymic reactions in a thermodynamically open system can.

Thus the philosophical stance taken in this book is the reductionist one, which in the present context amounts to the statement: "Notwithstanding the complexity of metabolic systems there are no 'hidden forces' that come into play when the system reaches a certain level of complexity." However, we acknowledge that an operational definition of complexity is not easy to formulate either!

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