Structure and flux analysis of metabolic networks

Kapitel i bok, 2009

Conceptual understanding of complex cellular organization can be facilitated through a perspective based on the central dogma of biology1 (Figure 17.1). Accordingly, information coded in a genome is translated into proteins via mRNA. Proteins play a variety of roles in a cell, including that of enzymes, which selectively catalyze chemical transformation between metabolites. Ensemble of all nongenetically encoded compounds (thus, excluding mRNA, proteins, etc.) and enzymes operating on them is generally referred to as a metabolic network.2 In essence, metabolic networks convert nutrients available from environment into fundamental building blocks for the synthesis of proteins, DNA, and other cellular components. By providing energy and building blocks for growth and maintenance of cells, metabolic networks play a central role in sustaining life. is key role of metabolic networks in cellular operations is evident by two facts. Firstly, the basic architecture of metabolic networks is largely conserved across several dierent species ranging from microscopic bacteria to humans.3 Second, cellular response and adaptation to genetic/environmental perturbations is oen mediated through or reected in the operation of metabolic networks.4 Although the structure of metabolic networks dier signicantly at local levels (e.g., specic pathway structures),3,5 their large-scale conservancy across dierent species implies common biochemical and evolutionary principles underlying their operation.6,7 Understanding such general principles has great implications for: (i) correlating and extrapolating knowledge across dierent species, especially from model organisms (such as yeast) to humans, (ii) devising rational strategies for metabolic engineering, iii) nding remedies for metabolism related diseases, and (iv) synthetic biology.