(515i) Circuitry of Enzyme Reaction Networks

Biological reaction networks involve hundreds of metabolites and mechanistic reaction steps, information on which is burgeoning as a result of recent advances in experimental and ab initio techniques. A key challenge is to develop a framework wherein such networks are quantitatively analyzed. We present a new graph-theoretic approach in which mechanistic reaction steps are represented by directed branches, while the nodes simply represent their interconnectivity, not necessarily individual species, such that all reaction pathways can be visualized simply as walks on the graph. This confers a unique and new architecture to these reaction route (RR) networks, allowing direct conversion into equivalent electrical circuits, and hence making them suitable for not only mechanistic insights but also rigorous flux and kinetic analysis via the vast array of tools available for electrical circuit analysis including Kirchhoff's current law (KCL) and Kirchhoff's potential law (KPL). The approach is illustrated with the help of conversion of 7,8-dihydrofolate (A) and NADPH (B) into 5,6,7,8-tetrahydrofolate (C) and NADP+ (D), catalyzed by the enzyme dihydrofolate reductase (DHFR) (E). Other examples of metabolic networks are also briefly mentioned.