Ch. 21: The Generation of Biochemical Energy

1. Ch. 21: The Generation of Biochemical Energy

2. Energy and Life • Energy can be converted from one form to another, but can be neither created nor destroyed. • All living organisms need energy to carry out various functions. • In humans, energy released from food allows us to do the various kinds of work that need to be done. • Energy used by almost all living organisms ultimately comes from the sun.

3. Energy & Life Cont. • Plants convert sunlight to potential energy stored mainly in the chemical bonds of carbohydrates. • Plant-eating animals utilize the energy stored by the plants (some for immediate needs and the rest to be stored for future needs, mainly in the form of chemical bonds in fats). • Other animals, including humans, are able to eat plants and animals and use the chemical energy these organisms have stored.

4. Energy Flow Through the Biosphere

5. Specific Energy Requirements • For energy to be useful in living organisms: • Energy must be released from food gradually. • Energy must be stored in readily available form. • The release of energy from storage must be finely controlled so that it is available when and where it is needed. • Just enough energy must be released as heat to maintain constant body temperature. • Energy must be available to drive chemical reactions that aren’t favorable at body temperature.

6. Energy and Biochemical Reactions • Chemical reactions in living organisms are no different than reactions in a chemical laboratory. • They either release energy (exothermic, DH is negative) or absorb energy (DH is positive) • They may be favorable (spontaneous, exergonic, DG is negative) and proceed on their own or nonfavorable (nonspontaneous, endergonic, DG is positive) and require constant input to continue. • Spontaneous reactions, those are favorable in the forward direction, release free energy and the energy released is available to do work. • Remember DG = DH - TDS • Spontaneous (exergonic) reactions are the source of our biochemical energy.

7. Exergonic vs. Endergonic Reactions spontaneous nonspontaneous

8. Exergonic vs. Endergonic Cont. • Products of exergonic reactions are more stable than the reactants and the free energy change DG has a negative value. • Oxidation reactions are usually favorable reactions and release energy. • Oxidation of glucose, the principal source of energy for animals, produces 686 kcal of free energy per mole of glucose. • Products of endergonic reactions are less stable than the reactants and the free energy ahange has a positive value. • Unfavorable reactions can’t occur without the input of energy from an outside source.

9. Photosynthesis in plants, converts CO2 and H2O to glucose plus O2 which is the reverse of oxidation of glucose. The sun provides the necessary external energy for photosynthesis (686 kcal of free energy per mole of glucose formed).

10. Problem • In photosynthesis, green plants convert carbon dioxide and water into glucose (C6H12O6) according to the equation: 6CO2(g) + 6H2O(l) + 678 kcal  C6H12O6(aq) + 6O2(g) a) Is the reaction exothermic or endothermic? endothermic b) What is the value of DH for the reaction? +678 kcal c) Write the equation for the reverse reaction, including heat as a reactant or product. C6H12O6(aq) + 6O2(g)  6CO2(g) + 6H2O(l) + 678 kcal

11. Cells and Their Structures • Energy generating reactions take place within the cells of living organisms. • There are mainly two kinds of cells: • - prokaryotic cells, usually found in single-celled organisms including bacteria and blue-green algae. • - eukaryotic cells, found in some single-celled organisms and all plants and animals.

12. Eukaryotic Cell • Eukaryotic cells are about 1000 times larger than bacteria cells. • They have a membrane enclosed nucleus containing their DNA • They have several other internal structures known as organelles that perform specialized tasks. • cytoplasm: the region between the cell membrane and the nuclear membrane in a eukaryotic cell • cytosol: the aqueous fluid part of the cytoplasm surrounding the organelles within a cell

13. Mitochondria • Often called the cell’s “power plant”. • mitochondrion (singular) or mitochondria (plural): an egg-shaped organelle where small molecules are broken down to provide the energy for an organism. • mitochondrial matrix: the space surrounded by the inner membrane of a mitochondrion • About 90% of the body’s principle energy carrying molecule adenosine triphosphate (ATP) is produced here. • Adenosine triphosphate (ATP): the principal energy-carrying molecule; removal of a phophoryl group to give ADP releases free energy.

14. The Mitochondrion

15. The Mitochondrion Cont. • Cells have many mitochondria. • The citric acid cycle takes place here. • Number is greatest in eye, brain, heart, and muscle cells where the need for energy is greatest. • People (such as athletes) who put heavy energy demands on their bodies develop an increased number of mitochondria. • All mitochondria in our bodies develop from those in the egg that was fertilized, meaning that only our mothers contribute our inherited mitochondrial DNA. • valuable in anthropological studies

16. An Overview of Metabolism and Energy Production • Metabolism: Together, all the chemical reactions that take place in an organism. • Most of these reactions occur in sequences of metabolic pathways. • These pathways may be linear, cyclic, or spiral (see p. 605) • linear pathway: the product of one reaction serves as the starting material for the next • cyclic pathway: a series of reactions that regenerates one of the first reactants • spiral pathway: the same set of enzymes progressively builds up or breaks down a molecule

17. Overview Cont. • Catabolism: Metabolic reaction pathways that break down food molecules and release biochemical energy. • Anabolism: Metabolic reaction pathways that build larger biological molecules (including those can store energy) from smaller pieces.

18. Food molecules undergo catabolism to provide energy. Eating provides fuel, breathing provides oxygen, and our bodies oxidize the fuel to extract energy.

19. 4 Stages 1) digestion enzymes in saliva, stomach, and small intestine convert the large molecules of lipids to glycerol plus long-chain carboxylic acids, carbohydrates to glucose and other sugars, and proteins to amino acids and triacylglycerols 2) acetyl-S-coenzyme A production the small molecules from digestion follow separate pathways that move their C atoms into 2-carbon acetyl groups. The acetyl groups are attached to coenzyme A by a bond between the sulfur atom of the thiol group at the end of the coenzyme A molecule and the carbonyl carbon atom of the acetyl group O ║ CH3 – C – S – [Coenzyme A] The resultant compound acetyl-S-coenzyme A (abbreviate acetylSCoA) is an intermediate in the breakdown of all classes of food molecules. It carries the acetyl groups into the common pathways of catabolism – stage 3, the citric acid cycle, and stage 4, electron transport and ATP production

20. 4 Stages Cont. 3) citric acid cycle -Within mitochondria, the acetyl-group C atoms are oxidized to the CO2 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 also leaves the cycle stored in the chemical bonds of ATP or a related triphosphate 4) ATP production -Electrons from the reduced coenzymes are passed from molecule to molecule down an electron-transport chain. Along the way, their energy is harnessed to produce more ATP. -At the end of the process these electrons, along with H+ from the reduced coenzymes, combine with oxygen that we breathe to produce water. Thus, the reduced coenzymes are in effect oxidized by atmospheric oxygen, while the energy that they carried is stored in the chemical bonds of ATP molecules.

22. Strategies of Metabolism: ATP and Energy Transfer • Adenosine triphosphate (ATP) transports energy in living organisms. • ATP has three –PO3- groups. (see p. 607) • Removal of one of the –PO3- groups from ATP by hydrolysis produces adenosine diphosphate (ADP). Since this reaction is an exergonic process, it releases energy. • The reverse of ATP hydrolysis reaction is known as phosphorylation reaction. Phosphorylation reactions are endergonic.

23. ATP & Energy Transfer Cont. • ATP is an energy transporter because its production from ADP requires an input of energy that is then released whenever the reverse reaction occurs. • Biochemical energy is gathered from exergonic reactions that produce ATP. The ATP then travels to where energy is needed, and ATP hydrolysis releases the energy for whatever work must take place. • ATP hydrolysis is slow if there is no catalysts. The stored energy is released only in the presence of the appropriate enzymes. • Biochemical energy production, transport, and use all depend upon the ATP/ADP interconversion.

24. ATP/ADP Interconversion

26. Strategies of Metabolism: Metabolic Pathways & Coupled Reactions • Metabolic pathways of catabolism release energy bit by bit in a series of reactions. • The overall reaction and the overall free-energy change for any series of reactions can be found by summing up the equations and the free-energy changes for the individual steps. • Some of the individual steps may be endergonic, but the sum of reactions of all metabolic pathways add up to favorable processes with negative (exergonic) free-energy changes.

27. Metabolic Pathways & Coupled Reactions Cont. • Metabolic strategy is to couple an energetically unfavorable step (endergonic) with an energetically favorable (exergonic) step so that the overall energy change for the two reactions is favorable. DG = +3.3 kcal/mol DG = - 7.3 kcal/mol DG = -4.0 kcal/mol

28. Reaction of Phosphenolpyruvate DG = -14.8 kcal/mol DG = + 7.3 kcal/mol DG = -7.5 kcal/mol For coupled reactions, a curved arrow often connects the reactants and products in one of the two chemical changes. The above reaction can be written…

29. Strategies of Metabolism: Oxidized and Reduced Coenzymes • The net result of catabolism is the oxidation of food molecules to release energy. • Many metabolic reactions are therefore oxidation-reduction reactions. • A steady supply of oxidizing and reducing agents must be available to accomplish the oxidation-reduction reactions.

30. Redox Reminders • 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.

31. A few enzymes continuously cycle between their oxidized and reduced forms.

32. NAD & NADP • Nicotinamide adenine dinucleotide (NAD) and its phosphate (NADP) are widespread coenzymes required for redox reactions. • As oxidizing agents (NAD+ and NADP+) they remove hydrogen from a substrate. • As reducing agents (NADH and NADP) they provide hydrogen that adds to a substrate. oxidation O

33. Reduction Example

34. Citric Acid Cycle • Citric acid cycle: The series of biochemical reactions that breaks down acetyl groups to produce energy carried by reduced coenzymes and carbon dioxide. • also called Krebs cycle • also called tricarboxylic acid cycle (TCA) • takes place in mitochondria • The eight steps of the cycle produce: • two molecules of CO2 (from conversion of an acetyl group) • four molecules of reduced coenzymes (3 NADH, 1 FADH2) • one energy rich phosphate (GTP) • The final step regenerates the reactant for step 1 of the next turn of the cycle.

35. Fig 21.9 The citric acid cycle

36. Kreb Cycle Steps Steps 1 & 2: set the stage for oxidation. Acetyl groups enter the cycle at step 1 by addition to 4-C oxaloacetate to give citrate (a 6-C intermediate). Citrate is a 3° alcohol and can’t be oxidized; it is converted in step 2 to its isomer isocitrate, a 2° alcohol which is oxidized to a ketone in step 3. The two steps of the isomerization are catalyzed by aconitase. Water is first removed and then added back to the intermediate, which remains in the active site, so that –OH is on a different carbon atom. Steps 3 & 4: 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 in the reduction of NAD+. The succinyl-SCoA carries 4 C atoms along to the step 5.

37. Kreb Cycle Steps Cont. step 5: The 4-C oxaloacetate must be restored for step 1 of the next cycle. The exergonic conversion of succinyl-SCoA to succinate is coupled with phosphorylation of guanosine diphosphate (GDP) to give guanosine triphosphate (GTP). GTP is similar in structure to ATP and carries energy that can be released during transfer of one of its phosphoryl groups. (Step 5 is the only step in the cycle that generates an energy-rich triphosphate). step 6: The succinate from step 5 is oxidized by removal of 2 H atoms to give fumarate. The enzyme for this reaction is part of the inner mitochondrial membrane. The reaction also requires the coenzyme FAD, which is covalently bound to its enzyme. This enzyme and FAD participate in stage 4 of catabolism by passing electrons directly into electron transport.

38. Kreb Cycle Cont. steps 7 & 8: The citric acid cycle is completed by regeneration of oxaloacetate, a reactant for step 1. Water is added across the double bond of fumarate to give malate (step 7) and oxidation of the malate, a 2 ° alcohol, gives the oxaloacetate (step 8).

39. The Krebs Cycle Operates As Long As… 1) acetyl groups are available from acetylSCoA 2) the oxidizing agent coenzymes NAD+ and FAD are available 3) oxygen is available

40. Electron-Transport Chain • In some ways catabolism is like burning gasoline. • The goal is to produce useful energy and the reaction products are water and CO2. • The difference is that in catabolism, the products are not released all at once, and not all of the energy is released as heat. • At the end of the citric acid cycle, the reduced coenzymes formed are ready to donate their energy to making more ATP. • The energy is released in a series of oxidation-reduction reactions that move electrons from one electron carrier to the next as each carrier is reduced (gains electrons from the preceding carrier) and then oxidized (loses an electron by passing it along to the next carrier)

41. The Electron-Transport Chain and ATP Production • Electron transport chain: The series of biochemical reactions that passes electrons from reduced coenzymes to oxygen and is coupled to ATP formation. • The electrons combine with the oxygen we breathe and with hydrogen ions from their surrounding to produce water. • O2 + 4e- + 4H+ 2 H2O • also called the “respiratory chain” • Electron transport involves four enzyme complexes held in fixed positions within the inner membrane of mitochondria and two electron carriers move from one complex to another.

42. The four enzymes involved in electron transport chain complexes are polypeptides and electron acceptors. Electron transport chain

43. Electron Acceptors • The most important electron acceptors are: • Various cyctochromes that contain heme groups in which the iron cycles between Fe2+ and Fe3+. • Proteins with iron-sulfur groups in which the iron also cycles between Fe2+ and Fe3+, and • The coenzyme Q, often known as ubiquinone because of its widespread occurrence and the presence of a quinone group in its structure.

44. Hydrogen from NADH enters electron transport chain at enzyme complex I. Electrons from FADH2 enter the chain at enzyme complex II. FADH2 is oxidized by reaction with coenzyme Z. Electrons are passed from weaker to increasingly stronger oxidizing agents, with energy released at each transfer. Hydrogen ions are released for transport through the inner membrane at complexes I, III, and IV. The H+ concentration difference creates a potential energy difference across the two sides of the inner membrane. • Fig 21.12 Pathway of electrons in electron transport

45. ATP Synthesis • oxidative phosphorylation: the synthesis of ATP from ADP using energy released in the electron-transport chain • ATP synthase: the enzyme complex in the inner mitochondrial membrane at which hydrogen ions cross the membrane and ATP is synthesized from ADP. • ADP is converted to ATP by a reaction between ADP and hydrogen phosphate ion. This is both an oxidation and phosphorylation reaction. Energy released in the electron transport chain drives this reaction forward. ADP + HOPO32- ATP + H2O

46. Harmful Oxygen By-Products and Antioxidant Vitamins • About 90% of the oxygen we breathe is utilized in the electron transport-ATP synthesis reactions. • These and other oxygen-consuming reactions produce some harmful oxygen-containing, highly reactive products • hydroxyl free radical, HO. • superoxide ion, O2-. • hydrogen peroxide, H2O2 • These reactive species can cause damage by breaking covalent bonds in enzymes and other proteins, DNA, and the lipids in the cell membranes.

47. The outcomes of such damages are cancer, liver damage, heart disease, immune system damage etc.

48. Superoxide dismutase and catalase, some very fast acting enzymes in our body, provide protection against these harmful free radicals and hydrogen peroxide by destroying them as they are produced. superoxide dismutase • 2O2-• + 2H+ ------------> H2O2 + O2 catalase • 2H2O2 -------------> 2H2O + O2 • Protection is also provided by the vitamins E, C, and A. These vitamins make the free radicals harmless by bonding with them.