Metabolism is a linked series of chemical reactions that begins with a particular biomolecule and converts it into some other required biomolecule in a carefully defined fashion (Figure 15.2). These metabolic pathways process a biomolecule from a starting point (glucose, for instance) to an end point (carbon dioxide, water, and biochemically useful energy, in regard to glucose) without the generation of wasteful or harmful side products. There are many such defined pathways in the cell (Figure 15.3), together called intermediary metabolism, and we will examine many of them in some detail later. These pathways are interdependent—a biochemical ecosystem—and their activities are coordinated by exquisitely sensitive means of communication in which allosteric enzymes are predominant. We considered the principles of this communication in Chapters 7 and 13.

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We can divide metabolic pathways into two broad classes: (1) those that convert energy from fuels into biologically useful forms, such as ATP or ion gradients, and (2) those that require inputs of energy to proceed. Although this division is often imprecise, it is nonetheless a useful distinction in an examination of metabolism. Those reactions that transform fuels into cellular energy are called catabolic reactions or, more generally, catabolism:

Those reactions that require energy—such as the synthesis of glucose, fats, or DNA—are called anabolic reactions or anabolism. The useful forms of energy that are produced in catabolism are employed in anabolism to generate complex structures from simple ones, or energy-rich states from energy-poor ones.

Some pathways can be either anabolic or catabolic, depending on the energy conditions in the cell. They are referred to as amphibolic pathways.

An important general principle of metabolism is that, although biosynthetic and degradative pathways often have reactions in common, the regulated, irreversible reactions of each pathway are almost always distinct from each other. This separation is necessary for energetic reasons, as will be evident in subsequent chapters. It also facilitates the control of metabolism.

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How are specific pathways constructed from individual reactions? A pathway must satisfy minimally two criteria: (1) the individual reactions must be specific, and (2) the entire set of reactions that constitute the pathway must be thermodynamically favored. A reaction that is specific will yield only one particular product or set of products from its reactants. For example, glucose can undergo step-by-step conversion to yield carbon dioxide and water as well as useful energy. This conversion is extremely energy efficient because each step is facilitated by enzymes—highly specific catalysts (Section 3). The thermodynamics of metabolism is most readily approached in relation to free energy, which was discussed in Chapter 6. A reaction can take place spontaneously only if ΔG, the change in free energy, is negative. Recall that ΔG for the formation of products C and D from substrates A and B is given by

Thus, the ΔG of a reaction depends on the nature of the reactants and products (expressed by the ΔG°′ term, the standard free-energy change) and on their concentrations (expressed by the second term).

An important thermodynamic fact is that the overall free-energy change for a chemically coupled series of reactions is equal to the sum of the free-energy changes of the individual steps. Consider the following reactions:

Under standard conditions, A cannot be spontaneously converted into B and C, because ΔG°′ is positive. However, the conversion of B into D under standard conditions is thermodynamically feasible. Because free-energy changes are additive, the conversion of A into C and D has a ΔG°′ of −13 kJ mol⁻¹ (−3 kcal mol⁻¹), which means that it can take place spontaneously under standard conditions. Thus, a thermodynamically unfavorable reaction can be driven by a thermodynamically favorable reaction to which it is coupled. In this example, the reactions are coupled by the shared chemical intermediate B. Metabolic pathways are formed by the coupling of enzyme-catalyzed reactions such that the overall free energy of the pathway is negative.