Metabolism, Energy, and Cellular Functions Overview

1. Outline 20.1 Energy and Life 20.2 Energy and Biochemical Reactions 20.3 Cells and Their Structure 20.4 An Overview of Metabolism and Energy Production 20.5 Strategies of Metabolism: ATP and Energy Transfer 20.6 Strategies of Metabolism: Metabolic Pathways and Coupled Reactions 20.7 Strategies of Metabolism: Oxidized and Reduced Coenzymes 20.8 The Citric Acid Cycle 20.9 The Electron Transport Chain and ATP Production 20.10 Harmful Oxygen By-Products and Antioxidant Vitamins

2. Goals • What is the source of our energy, and what is its fate in the body? Be able to provide an overview of the sources of our energy and how we use it, identify the cellular location of energy generation, and explain the significance of exergonic and endergonic reactions in metabolism. • How are the reactions that break down food molecules organized? Be able to list the stages in catabolism and describe the role of each. • What are the major strategies of metabolism? Be able to explain and give examples of the roles of ATP, coupled reactions, and oxidized and reduced coenzymes in metabolic pathways.

3. Goals • What is the citric acid cycle? Be able to describe what happens in the citric acid cycle and explain its role in energy production. • How is ATP generated in the final stage of catabolism? Be able to describe in general the electron-transport chain, oxidative phosphorylation, and how they are coupled. • What are the harmful by-products produced from oxygen, and what protects against them? Be able to identify the highly reactive oxygen-containing products formed during metabolism and the enzymes and vitamins that counteract them.

4. 20.1 Energy and Life • Living things do mechanical and chemical work, synthesizing molecules and moving them across cell membranes. • The energy used by all but a very few living things on earth comes from the sun. • Plants convert sunlight to potential energy stored in the bonds of carbohydrates. • Animals use this energy, and store the excess in the bonds of fats.

5. 20.1 Energy and Life

6. 20.1 Energy and Life • Our bodies have specific requirements for energy. • Energy must be released from food gradually. • Energy must be stored in accessible forms. • Release of energy must be finely controlled. • Just enough energy must be released as heat to maintain constant body temperature. • Energy must be available to drive chemical reactions that are not favorable at body temperature.

7. 20.2 Energy and Biochemical Reactions • Chemical reactions either release or absorb energy according to the formula: ΔG = ΔH – TΔS • Reactions in living organisms are no different from reactions in a chemistry laboratory.

8. 20.2 Energy and Biochemical Reactions • Spontaneous reactions release free energy. Exergonic reactions are the source of biochemical energy.

9. 20.2 Energy and Biochemical Reactions • The greater the amount of free energy released, the further a reaction proceeds toward product formation before reaching equilibrium. • Reactions requiring an input of energy are endergonic. • Free energy changes switch sign for the reverse of the reaction, but the value does not change.

10. 20.2 Energy and Biochemical Reactions • Living systems make use of this in biochemical pathways. • Energy is stored in the products of an overall endergonic reaction pathway. • This stored energy is released in an overall exergonic reaction pathway that regenerates the original reactants.

11. 20.2 Energy and Biochemical Reactions • Endergonic—A nonspontaneous reaction or process that absorbs free energy and has a positive ΔG. • Exergonic— A spontaneous reaction or process that releases free energy and has a negative ΔG.

12. 20.2 Energy and Biochemical Reactions Life without Sunlight • In 1977, hydrothermal vents—openings spewing water heated to 400 °C deep within the earth—were found on the ocean floor. The vents were dubbed “black smokers” because the water was black with mineral sulfides precipitating from the hot, acidic water as it exited the vents. • Distinctive types of bacteria form the basis for the web of life in these locations. What replaces sunlight as their source of energy? The hot water is rich in dissolved inorganic substances that are reducing agents and electron donors. Life-supporting energy is set free by their oxidation. • Carbon dioxide dissolved in the seawater is the raw material used by the bacteria to make their own essential carbon-containing biomolecules. • In 1991, scientists discovered a volcano erupting underneath the ocean. Initially, all life in the vicinity was wiped out, yet soon afterward, the area was thriving with bacteria. Could it be that a thriving population of bacteria has been living in the hot interior of the earth ever since it formed? Were these anaerobic bacteria earth’s first inhabitants, and could they exist beneath the surface of other planets? Research will eventually answer these questions.

13. 20.3 Cells and Their Structure • There are two main categories of cells: prokaryotic and eukaryotic. • Prokaryotic cells are usually found in single-celled organisms (bacteria, blue-green algae). • Eukaryotic cells are found in single-celled yeast, and in all plants and animals.

14. 20.3 Cells and Their Structure • Eukaryotic cells are about 1000 times larger than prokaryotic cells. • Features include: • Membrane-enclosed nucleus • Organelles are small, functional units that perform specific tasks. • Cytoplasm is the region between the cell and nuclear membranes. • Cytosol is the fluid part of the cytoplasm, with electrolytes, nutrients and enzymes in solution.

15. 20.3 Cells and Their Structure

16. 20.3 Cells and Their Structure

17. 20.3 Cells and Their Structure • Mitochondria, the cell’s “power plants,” are the most important of the organelles for energy production.

18. 20.3 Cells and Their Structure • The citric acid cycle takes place in the matrix. • Electron transport and ATP production take place at the inner surface of the inner membrane. • The numerous folds in the inner membrane—known as cristae—increase the surface area over which these pathways can take place.

19. 20.4 An Overview of Metabolism and Energy Production • All the chemical reactions that take place in an organism constitute its metabolism. • Most reactions occur in metabolic pathways.

20. 20.4 An Overview of Metabolism and Energy Production • Catabolism—Metabolic reaction pathways that break down food molecules and release biochemical energy. • Anabolism—Metabolic reactions that build larger biological molecules from smaller pieces.

21. 20.4 An Overview of Metabolism and Energy Production

22. 20.4 An Overview of Metabolism and Energy Production Stage 1: Digestion • Enzymes in saliva, the stomach, and the small intestine convert large molecules to smaller molecules. • Carbohydrates are broken down to glucose and other sugars. • Proteins are broken down to amino acids, and triacylglycerols. • Lipids are broken down to glycerol plus long-chain carboxylic acids, termed fatty acids. • These smaller molecules are transferred into the blood for transport to cells throughout the body.

23. 20.4 An Overview of Metabolism and Energy Production Stage 2: Acetyl-Coenzyme A production • The small molecules from digestion follow pathways that move their carbon atoms into two-carbon acetyl groups. • The acetyl groups are attached to coenzyme A by a bond between the sulfur of the thiol group on coenzyme A and the carbonyl carbon atom of the acetyl group. 

24. 20.4 An Overview of Metabolism and Energy Production Stage 2: Acetyl-Coenzyme A production • The small molecules from digestion follow pathways that move their carbon atoms into two-carbon acetyl groups. • Acetyl groups are attached to coenzyme A by a bond between sulfur of the thiol group on coenzyme A and the carbonyl carbon of the acetyl.  • Acetyl-CoA is an intermediate in the metabolism of all food molecules.

25. 20.4 An Overview of Metabolism and Energy Production Stage 3: Citric acid cycle • Within mitochondria, the acetyl-group carbon atoms are oxidized to the carbon dioxide that we exhale. • Most of the energy released in the oxidation leaves the citric acid cycle in the chemical bonds of reduced coenzymes (NADH, FADH2). • Some energy leaves the cycle stored in the chemical bonds of adenosine triphosphate (ATP) or a related triphosphate.

26. 20.4 An Overview of Metabolism and Energy Production Stage 4: ATP production • Electrons from the reduced coenzymes are passed from molecule to molecule down an electron-transport chain. • Their energy is harnessed to produce ATP. • At the end of the process, these electrons—along with hydrogen ions from the reduced coenzymes—combine with oxygen to produce water. • The reduced coenzymes are oxidized by atmospheric oxygen, and the energy that they carried is stored in the chemical bonds of ATP molecules.

27. 20.5 Strategies of Metabolism: ATP and Energy Transfer • ATP has three phosphate groups. • Removal of one of the –PO4 groups by hydrolysis gives adenosine diphosphate – ADP.

28. 20.5 Strategies of Metabolism: ATP and Energy Transfer • ATP is an energy transporter because its production from ADP requires an input of energy that is then released wherever the reverse reaction occurs. ATP + H2O ➝ ADP + Pi ΔG = –7.3 kcal/mol ADP + Pi ➝ ATP + H2O ΔG = +7.3 kcal/mol

29. 20.5 Strategies of Metabolism: ATP and Energy Transfer • The hydrolysis of ATP to give ADP and its reverse, the phosphorylation of ADP, are reactions perfectly suited to their role in metabolism. • The stored energy is released only in the presence of the appropriate enzymes. • A useful amount of energy is released when a phosphoryl group is removed from it by hydrolysis. • If too much energy was involved, interconversion would be more difficult.

30. 20.6 Strategies of Metabolism: Metabolic Pathways and Coupled Reactions • The overall free-energy change for any series of reactions can be found by summing up the free-energy changes for the individual steps. • Not every step in a metabolic pathway is downhill. • Energetically unfavorable reactions are coupled to energetically favorable reactions so that the overall energy change is favorable. • Coupling allows the energy stored in one chemical compound be transferred to other compounds. • Excess energy is released as heat and contributes to maintaining body temperature.

31. 20.6 Strategies of Metabolism: Metabolic Pathways and Coupled Reactions

32. 20.6 Strategies of Metabolism: Metabolic Pathways and Coupled Reactions Basal Metabolism • The minimum amount of energy expenditure required per unit of time to stay alive is basal metabolic rate. It can be measured by finding the rate of oxygen consumption, which is proportional to the energy used. • An average basal metabolic rate is 70 kcal/hr (293 kJ/hr), or about 1700 kcal/day (7100 kJ/day): 1 kcal/hr (4.2 kJ/hr) per kilogram of body weight by a male and 0.95 kcal/hr (4 kJ/hr) per kilogram of body weight by a female. • The total calories a person needs each day is determined by basal requirements plus energy used in additional physical activities. • A relatively inactive person requires about 30% above basal requirements per day, a lightly active person requires about 50% above basal, and a very active person can use 100% above basal requirements in a day. • Each day that you consume food with more calories than you use, the excess calories are stored as potential energy in the chemical bonds of fats in your body and your weight rises. Each day that you consume food with fewer calories than you burn, some chemical energy in your body is taken out of storage to make up the deficit.

33. 20.7 Strategies of Metabolism: Oxidized and Reduced Coenzymes • Many metabolic reactions are oxidation–reduction reactions. • A steady supply of oxidizing and reducing agents must be available. • A few coenzymes cycle continuously between their oxidized and reduced forms.

34. 20.7 Strategies of Metabolism: Oxidized and Reduced Coenzymes • Oxidation can be loss of electrons, loss of hydrogen, or addition of oxygen. • Reduction can be gain of electrons, gain of hydrogen, or loss of oxygen. • Oxidation and reduction always occur together. • Each increase in the number of carbon–oxygen bonds is an oxidation, and each decrease in the number of carbon–hydrogen bonds is a reduction.

35. 20.7 Strategies of Metabolism: Oxidized and Reduced Coenzymes • Nicotinamide adenine dinucleotide and its phosphate are coenzymes that enter and leave enzyme active sites in which they are required for redox reactions. • As oxidizing agents they remove hydrogen from a substrate, and as reducing agents (NADH and NADPH) they provide hydrogen that adds to a substrate.

36. 20.7 Strategies of Metabolism: Oxidized and Reduced Coenzymes • The oxidation of malate to oxaloacetate requires the removal of two hydrogen atoms to convert a secondary alcohol to a ketone. • The oxidizing agent, which will be reduced during the reaction, is NAD+ functioning as a coenzyme for the enzyme malate dehydrogenase.

37. 20.7 Strategies of Metabolism: Oxidized and Reduced Coenzymes • A hydrogen atom is equivalent to a hydrogen ion, H+ plus an electron, e–. • Flavin adenine dinucleotide (FAD), another common oxidizing agent, is reduced by the formation of covalent bonds to two hydrogen atoms to give FADH2.

38. 20.7 Strategies of Metabolism: Oxidized and Reduced Coenzymes • Because reduced coenzymes have picked up electrons (in their bonds to hydrogen) that are passed along in subsequent reactions, they are often referred to as electron carriers. • As coenzymes cycle through their oxidized and reduced forms, they also carry energy along from reaction to reaction. • Ultimately, this energy is passed on to the bonds in ATP.

39. 20.8 The Citric Acid Cycle • The acetyl groups in acetyl-SCoA molecules are readily removed in an energy-releasing hydrolysis reaction.

40. 20.8 The Citric Acid Cycle • Oxidation of 2 carbons to give CO2 and transfer of energy to reduced coenzymes occurs in the citric acid cycle. • This is also known as the tricarboxylic acid cycle (TCA) or Krebs cycle. • The citric acid cycle is a closed loop of reactions in which the product of the final step, oxaloacetate, is the reactant in the first step.

41. 20.8 The Citric Acid Cycle

42. 20.8 The Citric Acid Cycle STEPS 1 and 2: • Acetyl groups enter the cycle at Step 1 by addition to 4-carbon oxaloacetate to give citrate, a 6-carbon intermediate. • Citrate is a tertiary alcohol and cannot be oxidized; it is converted in Step 2 to its isomer, isocitrate, a secondary alcohol that can be oxidized to a ketone. The isomerization is catalyzed by aconitase.

43. 20.8 The Citric Acid Cycle STEPS 3 and 4: • Both steps are oxidations that rely on NAD+ as the oxidizing agent. • One CO2 leaves at Step 3 as the —OH group of isocitrate is oxidized to a keto group. • A second CO2 leaves at Step 4, and the resulting succinyl group is added to coenzyme A. In both steps, electrons and energy are transferred. • Succinyl-CoA carries four carbon atoms along to the next step.

44. 20.8 The Citric Acid Cycle STEP 5: • The 4-carbon oxaloacetate must be restored for Step 1 of the next cycle. • The exergonic conversion of succinyl-CoA to succinate is coupled with phosphorylation of GDP to give GTP. GTP is similar in structure to ATP and, like ATP, carries energy. • In many cells, GTP is directly converted to ATP. Step 5 is the only step in the cycle that generates an energy-rich triphosphate.

45. 20.8 The Citric Acid Cycle STEP 6: • Succinate from Step 5 is oxidized by removal of two hydrogen atoms to give fumarate. • The enzyme for this reaction, succinate dehydrogenase, is part of the inner mitochondrial membrane. • The reaction requires FAD, which is covalently bound to its enzyme. • Succinate dehydrogenase and FAD pass electrons directly into electron transport. • Step 6 neither uses nor releases energy.

46. 20.8 The Citric Acid Cycle STEPS 7 and 8: • Water is added across the double bond of fumarate to give malate (Step 7). • Oxidation of malate, a secondary alcohol, gives oxaloacetate (Step 8).

47. 20.8 The Citric Acid Cycle • The rate of the citric acid cycle is controlled by the body’s need for ATP and coenzymes. • When energy is being used at a high rate, ADP accumulates and activates isocitrate dehydrogenase, the enzyme for Step 3. • When the body’s supply of energy is abundant, NADH is present in excess and acts as an inhibitor of isocitrate dehydrogenase. • The cycle is activated when energy is needed and inhibited when energy is in good supply.

48. 20.9 The Electron-Transport Chain and ATP Production • At the conclusion of the citric acid cycle, the reduced coenzymes are ready to donate their energy to making ATP. • The energy is released in a series of oxidation–reduction reactions that move electrons from one carrier to the next. • Each reaction in the series is exergonic.

49. 20.9 The Electron-Transport Chain and ATP Production • The sequence of reactions is known as the electron-transport chain (also the respiratory chain). • The enzymes and coenzymes of the chain are embedded in the inner membrane of the mitochondrion.

50. 20.9 The Electron-Transport Chain and ATP Production • As electrons move down the electron-transport pathway, the energy is used to move hydrogen ions from the matrix into the intermembrane space. • Because the inner membrane is otherwise impermeable to the H+ ion, the result is a higher H+ concentration in the intermembrane space than in the mitochondrial matrix. • Moving ions from a region of lower concentration to one of higher concentration requires energy to make it happen. • This energy is recaptured for use in ATP synthesis.