Biochemistry Past Paper PDF

## Anabolism ### 10.2.01 Anabolism Uses Energy to Produce Structural and Storage Molecules Lesson 10.1 describes catabolism as the breakdown of large biomolecules, which permits storage of potential energy in various forms, including the high-energy chemical bonds of ATP, the redox potential of NA...

## Anabolism ### 10.2.01 Anabolism Uses Energy to Produce Structural and Storage Molecules Lesson 10.1 describes catabolism as the breakdown of large biomolecules, which permits storage of potential energy in various forms, including the high-energy chemical bonds of ATP, the redox potential of NADH, and the membrane potential that results from electrochemical gradients of ions. In contrast, this lesson discusses anabolism, which uses those different forms of energy currency to build larger biomolecules (Figure 10.15). | | | | | :------------- | :-------- | :-------- | | **Cell Macromolecules** | **Anabolism** | **Precursor Molecules** | | Proteins | Build up | Amino acids | | Polysaccharides | | Sugars | | Lipids | | Fatty acids | | Nucleic Acids | | Nitrogenous bases | | ADP + P | produced | NADH | | | | NADPH | | | | ATP consumed | | | | FADH2 | **Figure 10.15** Anabolic metabolism involves the use of energy to build larger biomolecules from smaller precursors. Concept 10.1.03 explains that the potential energy stored in energy currencies (particularly in ATP or ATP equivalents) can be coupled to endergonic processes. Anabolic applications of these coupled reactions can be used to build larger structural molecules or molecules that store excess energy. For example, protein translation couples GTP hydrolysis to peptide bond formation. Polysaccharide and glycerophospholipid synthesis use an NTP to "activate" monomeric precursors before formation of the glycosidic bond or ester linkage, respectively. Nucleic acid synthesis transfers an incoming nucleotide onto a growing strand, breaking the phosphoanhydride linkages of the incoming NTP or dNTP in the process. In all these cases, energy from an NTP is liberated to build larger molecules with distinct structural and functional purposes. Alternately, anabolism can be used to store excess energy. Organic fuels that have not been completely oxidized to *CO2* can instead be converted to glucose or fatty acids. Although energy is required to build these molecules, their complete oxidation later liberates much more energy (mostly in the form of ATP) than the amount of energy invested into building them. For example, the energy required to link glucose molecules to form glycogen is less than the energy released by converting glycogen back to glucose and then continuing to oxidize glucose to *CO2* through glycolysis and aerobic respiration. By storing energy in molecules such as glycogen or triglycerides, organisms can conserve fuel obtained during a feast and use them during periods of fasting or famine when fuel is less abundant, as shown in Figure 10.16. ### Fed State - Digested dietary nutrients - Anabolism - Glycogen synthesis in liver - Triglyceride storage in adipose tissue ### Fasting State - Liver glycogen - Catabolism - Free fatty acid (bound to carrier protein) - Free glucose - Glycogen and triglyceride stores broken down to supply energy - Adipose triglycerides **Figure 10.16:** Glycogen and triglycerides are energy-storage molecules that are synthesized through anabolic metabolism in the fed state. They are broken down to supply energy for the body during fasting. Just as catabolism can produce different forms of energy currency (see Concept 10.1.01), anabolism can utilize different forms of energy currency. NTPs are the most common form of energy currency; however, energy stored in the electrochemical potential of the proton gradient is used to synthesize ATP from ADP + *P*1 in the mitochondria. Redox cofactors such as NADPH are used in the synthesis of fatty acids and other lipids from acetyl-CoA. ### Catabolic and Anabolic Processes Must Be Regulated to Prevent Wasting Energy Energy capture from biomolecule catabolism is rarely 100% efficient. In addition, the anabolic building of molecules can waste energy. Thermodynamically, these inefficient reactions can be identified as those with large, negative Δ*G* values for the net reaction. A large, negative Δ*G* value means two things: 1) that at least some energy was not captured or stored in a usable form, and 2) that the reaction is biochemically irreversible. For example, glycolysis (see Chapter 11) includes two ATP-producing steps. The first, catalyzed by phosphoglycerate kinase, has a small, near-equilibrium Δ*G* (Δ*G* ≈ 0.09 kJ/mol), indicating that the energy of its acyl phosphate hydrolysis is efficiently captured in ATP condensation. However, the second ATP-producing step, catalyzed by pyruvate kinase, has a Δ*G* of much larger magnitude (Δ*G* ≈ -23.0 kJ/mol). Although some of the energy of the enol phosphate hydrolysis is captured in ATP condensation, approximately 23 kilojoules per mole is not captured (Figure 10.17). **Figure 10.17:** Exergonic reactions release energy. The anabolic counterpart of glycolysis is gluconeogenesis (see Chapter 11). Gluconeogenesis uses many of the same enzymes as glycolysis, but because certain enzymes catalyze irreversible reactions, enzymes that catalyze bypass reactions must be used instead. For example, gluconeogenesis cannot use pyruvate kinase to help build glucose because the pyruvate kinase reaction is irreversible. Instead, gluconeogenesis uses a pair of bypass reactions, catalyzed by pyruvate carboxylase and phosphoenolpyruvate carboxykinase (PEPCK), to convert pyruvate to phosphoenolpyruvate (Figure 10.18). Both bypass reactions are also highly exergonic (ie, large, negative Δ*G*). **Figure 10.18:** To circumvent the irreversible reaction catalyzed by pyruvate kinase, gluconeogenesis uses pyruvate carboxylase and phosphoenolpyruvate carboxykinase to catalyze bypass reactions. Therefore, both the catabolic process of glycolysis and the anabolic process of gluconeogenesis involve reactions that result in uncaptured energy. This is indicated by the energetic yield and cost of each process, respectively. One molecule of glucose undergoing glycolysis yields 2 pyruvate, 2 NADH, and 2 net molecules of ATP. In contrast, synthesis of one molecule of glucose through gluconeogenesis consumes 2 pyruvate, 2 NADH, and 6 molecules of ATP. Although the amount of pyruvate and NADH produced by glycolysis is the same as the amount consumed by gluconeogenesis, the difference in ATP amounts means energy is lost every time gluconeogenesis occurs. This also means that cells must regulate these processes to prevent a catabolic process and its anabolic counterpart from happening at the same time. A cell undergoing both glycolysis and gluconeogenesis at the same time would cycle glucose between both processes with a net cost of 4 ATP per cycle and no gain (Figure 10.19). This unregulated cycling between a catabolic process and its anabolic counterpart is known as a futile cycle or a substrate cycle. **Figure 10.19:** If glycolysis and gluconeogenesis took place simultaneously, the result would be a futile cycle that wastes energy without any material gain. In the subsequent chapters of this unit, a common theme in the regulation of metabolic processes is the reciprocal regulation of catabolic and anabolic counterparts to prevent futile cycles. This regulation can be accomplished through allosteric means, with the metabolites themselves acting as allosteric effectors. Regulation can also be the result of external, hormonal signals. Keeping in mind the biological logic of preventing futile cycles can help to simplify the understanding of the complex interplay of metabolic regulation.