ABSTRACT
We first encountered metabolic networks in Chapter 1. Unlike the physical interaction networks discussed in the two previous chapters, metabolic networks are somewhat more abstract. From the discussion in Chapter 1, we know that metabolic pathways depict series of chemical reactions that modify chemical substances (metabolites) and in the process synthesize the basic building blocks of the cell, including nucleic acids, amino acids, and fatty acids. By breaking down metabolites, these reactions use the energy stored in chemical bonds. Thus each edge in a metabolic network is a meta-edge comprising at least three individual physical interactions: enzymei-substrate, enzymei-product, product-enzymei+1, where the product is really the substrate of the next enzyme in the pathway (Figure 4.1). The concentrations of the various entities that make up metabolic networks are governed by the chemical rate equations for the reactions these entities participate in, and the form of these rate equations is in turn determined by the connectivity diagram (topology) and stoichiometry of the components of the metabolic network. The edges of a metabolic network may be bi-or unidirectional depending on the particular rates and equilibrium constants of the individual reactions (Box 4.1). Metabolic networks are special because they offer a direct testing
ground for the connection between genotype and phenotype. At the genotypic level, a gene encodes a particular enzyme, and changes in gene expression therefore lead to changes in the concentrations of the corresponding enzyme products. If detailed reaction parameters for all of the reactions these enzymes catalyze are known, one can predict the corresponding changes in metabolite levels. These changes often lead to phenotypical changes in the organism of interest. For example, reduced expression of enzymes that characterize anabolic reactions will lead to low reaction rates for these reactions and therefore to slow cell growth. In a more complex example, consider a mutation in the gene for the en-
FIGURE 4.1: A schematic diagram of a metabolic pathway. The three reactions at the top-enzyme E1 and substrate S1 forming a complex, conversion of substrate into product P1, followed by dissociation of E1 and P1-are represented in a metabolic network as a single “meta-edge” depicting the conversion of substrate S1 into product P1, which, in turn, acts as a substrate for the next reaction in the pathway.
