Part l Bioenergetics and Metabolism molecules, including lipids, polysaccharides, proteins, simultaneous synthesis and degradation of fatty acids and nucleic acids. Anabolic reactions require an input would be wasteful, however, and this is prevented by of energy, generally in the form of the phosphoryl group reciprocally regulating the anabolic and catabolic reac. transfer potential of ATP and the reducing power of tion sequences: when one sequence is active, the other NADH, NADPH, and FADH2(Fig 3) is suppressed. Such regulation could not occur if ana- Some metabolic pathways are linear, and some are bolic and catabolic pathways were catalyzed by exactly branched, yielding multiple useful end products from a the same set of enzymes, operating in one direction for single precursor or converting several starting materi- anabolism, the opposite direction for catabolism: inhi- als into a single product. In general, catabolic pathways bition of an enzyme involved in catabolism would also are convergent and anabolic pathways divergent(Fig. inhibit the reaction sequence in the anabolic direction. 4). Some pathways are cyclic: one starting component Catabolic and anabolic pathways that connect the same of the pathway is regenerated in a series of reactions two end points (glucose - pyruvate and pyruvate that converts another starting component into a prod- >glucose, for example) may employ many of the uct. We shall see examples of each type of pathway in same enzymes, but invariably at least one of the steps the following chapters. is catalyzed by different enzymes in the catabolic and Most cells have the enzymes to carry out both the anabolic directions, and these enzymes are the sites of degradation and the synthesis of the important cate- separate regulation. Moreover, for both anabolic and gories of biomolecules-fatty acids, for example. The catabolic pathways to be essentially irreversible, the re- actions unique to each direction must include at least one that is thermodynamically very favorable-in other words, a reaction for which the reverse reaction is very Cell unfavorable. As a further contribution to the separate macromolecules nutrients regulation of catabolic and anabolic reaction sequences, paired catabolic and anabolic pathways commonly take place in different cellular compartments: for example, Nucleic acids Proteins fatty acid catabolism in mitochondria, fatty acid syn- thesis in the cytosol. The concentrations of intermedi ates, enzymes, and regulators can be maintained at different levels in these different compartments. Be- cause metabolic pathways are subject to kinetic con- ADP +hPo2- trol by substrate concentration, separate pools of anabolic and catabolic intermediates also contribute to the control of metabolic rates. Devices that separate processes will be of particular nterest in our discussions of metabolism Catabolism NADH Metabolic pathways are regulated at several levels. NADPH from within the cell and from outside the most imme- FADH diate regulation is by the availability of substrate; when is near or below Km (as is commonly the case), the rate Chemical of the reaction depends strongly upon substrate con- centration(see Fig. 6-11). A second type of rapid con- trol from within is allosteric regulation(p. 225) by metabolic intermediate or coenzyme-an amino acid or Precursor Energy ATP, for example-that signals the cells internal meta bolic state. When the cell contains an amount of, say end products aspartate sufficient for its immediate needs, or when the cellular level of atp indicates that further fuel con- Nitrogenous bases sumption is unnecessary at the moment, these signals allosterically inhibit the activity of one or more enzymes in the relevant pathway In multicellular organisms the 3 Energy relationships between catabolic and anabolic metabolic activities of different tissues are regulated and ays Catabolic pathways deliver chemical energy in the form integrated by growth factors and hormones that act from of ATP, NADH, NADPH, and FADH2. These energy carriers are used outside the cell. In some cases this regulation occurs in anabolic pathways to convert small precursor molecules into cell virtually instantaneously(sometimes in less than a mil lisecond)through changes in the levels of intracellularmolecules, including lipids, polysaccharides, proteins, and nucleic acids. Anabolic reactions require an input of energy, generally in the form of the phosphoryl group transfer potential of ATP and the reducing power of NADH, NADPH, and FADH2 (Fig. 3). Some metabolic pathways are linear, and some are branched, yielding multiple useful end products from a single precursor or converting several starting materi￾als into a single product. In general, catabolic pathways are convergent and anabolic pathways divergent (Fig. 4). Some pathways are cyclic: one starting component of the pathway is regenerated in a series of reactions that converts another starting component into a prod￾uct. We shall see examples of each type of pathway in the following chapters. Most cells have the enzymes to carry out both the degradation and the synthesis of the important cate￾gories of biomolecules—fatty acids, for example. The simultaneous synthesis and degradation of fatty acids would be wasteful, however, and this is prevented by reciprocally regulating the anabolic and catabolic reac￾tion sequences: when one sequence is active, the other is suppressed. Such regulation could not occur if ana￾bolic and catabolic pathways were catalyzed by exactly the same set of enzymes, operating in one direction for anabolism, the opposite direction for catabolism: inhi￾bition of an enzyme involved in catabolism would also inhibit the reaction sequence in the anabolic direction. Catabolic and anabolic pathways that connect the same two end points (glucose n n pyruvate and pyruvate n n glucose, for example) may employ many of the same enzymes, but invariably at least one of the steps is catalyzed by different enzymes in the catabolic and anabolic directions, and these enzymes are the sites of separate regulation. Moreover, for both anabolic and catabolic pathways to be essentially irreversible, the re￾actions unique to each direction must include at least one that is thermodynamically very favorable—in other words, a reaction for which the reverse reaction is very unfavorable. As a further contribution to the separate regulation of catabolic and anabolic reaction sequences, paired catabolic and anabolic pathways commonly take place in different cellular compartments: for example, fatty acid catabolism in mitochondria, fatty acid syn￾thesis in the cytosol. The concentrations of intermedi￾ates, enzymes, and regulators can be maintained at different levels in these different compartments. Be￾cause metabolic pathways are subject to kinetic con￾trol by substrate concentration, separate pools of anabolic and catabolic intermediates also contribute to the control of metabolic rates. Devices that separate anabolic and catabolic processes will be of particular interest in our discussions of metabolism. Metabolic pathways are regulated at several levels, from within the cell and from outside. The most imme￾diate regulation is by the availability of substrate; when the intracellular concentration of an enzyme’s substrate is near or below Km (as is commonly the case), the rate of the reaction depends strongly upon substrate con￾centration (see Fig. 6–11). A second type of rapid con￾trol from within is allosteric regulation (p. 225) by a metabolic intermediate or coenzyme—an amino acid or ATP, for example—that signals the cell’s internal meta￾bolic state. When the cell contains an amount of, say, aspartate sufficient for its immediate needs, or when the cellular level of ATP indicates that further fuel con￾sumption is unnecessary at the moment, these signals allosterically inhibit the activity of one or more enzymes in the relevant pathway. In multicellular organisms the metabolic activities of different tissues are regulated and integrated by growth factors and hormones that act from outside the cell. In some cases this regulation occurs virtually instantaneously (sometimes in less than a mil￾lisecond) through changes in the levels of intracellular Part II Bioenergetics and Metabolism 483 Precursor molecules Amino acids Sugars Fatty acids Nitrogenous bases Energy￾containing nutrients Carbohydrates Fats Proteins Anabolism ATP NADH NADPH FADH2 Catabolism Chemical energy ADP HPO2 NAD NADP FAD 4 Cell macromolecules Proteins Polysaccharides Lipids Nucleic acids Energy￾depleted end products CO2 H2O NH3 FIGURE 3 Energy relationships between catabolic and anabolic pathways. Catabolic pathways deliver chemical energy in the form of ATP, NADH, NADPH, and FADH2. These energy carriers are used in anabolic pathways to convert small precursor molecules into cell macromolecules.