Biochemical Engineering Fundamentals, Part 1 - Bailey J., Ollis D. 1989

Stoichiometry and Energetics of Metabolic Transformations
Organization and Regulation of Metabolism
Key Intersection and Branching Points of Metabolic Pathways

Analyzing metabolic pathways as directed reaction networks allows us to identify the key elements of their Organization. An unbranched sequence of metabolic reactions is characteristic of a series of interrelated transformations within a given pathway. The initial and final substances of an unbranched pathway represent either starting nutrients, End products of METABOLISM (which in turn may be retained within The Cell or excreted into the environment), or, finally, precursors for other metabolic pathways, i.e., branch points. Typically, the first irreversible reaction following a branch point of a metabolic pathway (i.e., one having a substantially large negative ∆G' under intracellular conditions) serves as an allosterically regulated step. In this case, by regulating the influx of starting Materials, the cell distributes metabolites that are simultaneously used for multiple purposes. From a structural standpoint, these metabolites act as starting points or nodal junctions of the metabolic branch. It follows that branch points and modulated irreversible reactions are the critical elements determining all aspects of the cell's chemical activity. We will return to this issue repeatedly in subsequent sections and chapters, applying the principles outlined above to a simplified technological interpretation of The Cell as a chemical Reactor.

First of all, let us emphasize Structure/19.html">The Importance of branched reaction schemes from the most general perspective. It turns out that all types of cellular metabolic activity depend on the flux distribution of three primary Reagents: glucose-6-phosphate, Pyruvate, and acetyl-CoA. Fig. 5.24 schematically illustrates the intersections of Various metabolic pathways where these reagents serve as starting or end substances. The volume of flux through each pathway is regulated by the cell in accordance with its metabolic demands and current composition.

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FIG. 5.24. Schematic diagram of the intersection of major carbon metabolism pathways. In mammalian Cells, The conversion of acetyl-CoA to pyruvate does not occur.

As a more specific example, we can analyze the branched pathways of Amino acid Biosynthesis shown in Fig. 5.12. Here, too, one's attention is drawn to the presence of nodal points that serve as starting points for direct sequences of reactions, which subsequently branch out in their turn. In the next section, we will examine the localization of regulatory centers in this part of the metabolic network.