1. 26 26-1 © 2003 Thomson Learning, Inc. All rights reserved General, Organic, and Biochemistry, 7e Bettelheim, Brown, and March

2. 26 26-2 © 2003 Thomson Learning, Inc. All rights reserved Chapter 26 Bioenergetics How the Body Converts Food to Energy

3. 26 26-3 © 2003 Thomson Learning, Inc. All rights reserved Metabolism Metabolism: Metabolism: the sum of all chemical reactions involved in maintaining the dynamic state of a cell or organism pathway:pathway: a series of biochemical reactions catabolism:catabolism: the biochemical pathways that are involved in generating energy by breaking down large nutrient molecules into smaller molecules with the concurrent production of energy anabolism: anabolism: the pathways by which biomolecules are synthesized

4. 26 26-4 © 2003 Thomson Learning, Inc. All rights reserved Metabolism metabolism is the sum of catabolism and anabolism

5. 26 26-5 © 2003 Thomson Learning, Inc. All rights reserved Cells and Mitochondria Animal cells have many components, each with specific functions; some components along with one or more of their functions are: nucleus:nucleus: where replication of DNA takes place lysosomes:lysosomes: remove damaged cellular components and some unwanted foreign materials Golgi bodies:Golgi bodies: package and process proteins for secretion and delivery to other cellular components mitochondria:mitochondria: responsible for generation of most of the energy for cells see also Figure 26.2, next screen

6. 26 26-6 © 2003 Thomson Learning, Inc. All rights reserved A Rat Liver Cell

7. 26 26-7 © 2003 Thomson Learning, Inc. All rights reserved A Mitochondrion Schematic of a mitochondrion cut to reveal its inner organization

8. 26 26-8 © 2003 Thomson Learning, Inc. All rights reserved Common Catabolic Pthwy The two parts to the common catabolic pathway citric acid cyclecitric acid cycle, also called the tricarboxylic acid or Krebs cycle oxidative phosphorylationoxidative phosphorylation, also called the electron transport chain, or the respiratory chain The four principal compounds participating in the common catabolic pathway are: AMP, ADP, and ATP NAD + /NADH FAD/FADH 2 coenzyme A; abbreviated CoA or CoA-SH

9. 26 26-9 © 2003 Thomson Learning, Inc. All rights reserved Adenosine Triphosphate ATP ATP is the most important compound involved in the transfer of phosphate groups ATP contains two phosphoric anhydride bonds and one phosphoric ester bond

10. 26 26-10 © 2003 Thomson Learning, Inc. All rights reserved Adenosine Triphosphate hydrolysis of the terminal phosphate of ATP gives ADP, phosphate ion, and energy hydrolysis of a phosphoric anhydride liberates more energy than hydrolysis of a phosphoric ester we say that ATP and ADP contain high-energy phosphoric anhydride bonds ATP is a universal carrier of phosphate groups it is also a common currency for the storage and transfer of energy

11. 26 26-11 © 2003 Thomson Learning, Inc. All rights reserved NAD + /NADH 2 Nicotinamide adenine dinucleotide (NAD + ) Nicotinamide adenine dinucleotide (NAD + ) is a biological oxidizing agent

12. 26 26-12 © 2003 Thomson Learning, Inc. All rights reserved NAD + /NADH NAD + is a two-electron oxidizing agent, and is reduced to NADH NADH is a two-electron reducing agent, and is oxidized to NAD + NAD + and NADH are also hydrogen ion transporting molecules

13. 26 26-13 © 2003 Thomson Learning, Inc. All rights reserved FAD/FADH 2 Flavin adenine dinucleotide (FAD) Flavin adenine dinucleotide (FAD) is also a biological oxidizing agent

14. 26 26-14 © 2003 Thomson Learning, Inc. All rights reserved FAD/FADH 2 FAD is a two-electron oxidizing agent, and is reduced to FADH 2 FADH 2 is a two-electron reducing agent, and is oxidized to FAD

15. 26 26-15 © 2003 Thomson Learning, Inc. All rights reserved Coenzyme A Coenzyme A (CoA) Coenzyme A (CoA) is an acetyl-carrying group like NAD + and FAD, coenzyme A contains a unit of ADP CoA-SHCoA is often written CoA-SH to emphasize the fact that it contains a sulfhydryl group the vitamin part of coenzyme A is pantothenic acid the acetyl group of acetyl CoA is bound as a high- energy thioester

16. 26 26-16 © 2003 Thomson Learning, Inc. All rights reserved Citric Acid Cycle overview: the two carbon acetyl group of acetyl CoA is fed into the cycle and oxidized to 2 CO 2 there are four oxidation steps in the cycle

17. 26 26-17 © 2003 Thomson Learning, Inc. All rights reserved Citric Acid Cycle Step 1: condensation of acetyl CoA with oxaloacetate the high-energy thioester of acetyl CoA is hydrolyzed this hydrolysis provides the energy to drive Step 1 citrate synthase is an allosteric enzyme; it is inhibited by NADH, ATP, and succinyl-CoA

18. 26 26-18 © 2003 Thomson Learning, Inc. All rights reserved Citric Acid Cycle Step 2: dehydration and rehydration, catalyzed by aconitase, gives isocitrate citrate is achiral; it has no stereocenter aconitate is also achiral isocitrate is chiral; it has 2 stereocenters and 4 stereoisomers are possible only one of the 4 possible stereoisomers is formed in the cycle

19. 26 26-19 © 2003 Thomson Learning, Inc. All rights reserved Citric Acid Cycle Step 3: oxidation of isocitrate followed by decarboxylation gives  -ketoglutarate isocitrate dehydrogenase is an allosteric enzyme; it is inhibited by ATP and NADH, and activated by ADP and NAD +

20. 26 26-20 © 2003 Thomson Learning, Inc. All rights reserved Citric Acid Cycle Step 4: oxidative decarboxylation of  - ketoglutarate to succinyl-CoA the two carbons of the acetyl group of acetyl CoA are still present in succinyl CoA and in succinate this multienzyme complex is inhibited by ATP, NADH, and succinyl CoA; it is activated by ADP and NAD +

21. 26 26-21 © 2003 Thomson Learning, Inc. All rights reserved Citric Acid Cycle Step 5: formation of succinate the two CH 2 -COO - groups of succinate are now equivalent this is the first energy-yielding step of the cycle; a molecule of GTP is produced

22. 26 26-22 © 2003 Thomson Learning, Inc. All rights reserved Citric Acid Cycle Step 6: oxidation of succinate to fumarate Step 7: hydration of fumarate to L-malate L-malate is chiral and can exist as a pair of enantiomers; it is produced in the citric acid cycle as a single stereoisomer

23. 26 26-23 © 2003 Thomson Learning, Inc. All rights reserved Citric Acid Cycle Step 8: oxidation of malate oxaloacetate now can react with acetyl CoA to start another round of the cycle by repeating Step 1 The overall reaction of the cycle is

24. 26 26-24 © 2003 Thomson Learning, Inc. All rights reserved Citric Acid Cycle Control of the cycle controlled by three feedback mechanisms citrate synthase:citrate synthase: inhibited by ATP, NADH, and succinyl CoA; also product inhibition by citrate isocitrate dehydrogenase:isocitrate dehydrogenase: activated by ADP and NAD +, inhibited by ATP and NADH  -ketoglutarate dehydrogenase complex:  -ketoglutarate dehydrogenase complex: inhibited by ATP, NADH, and succinyl CoA; activated by ADP and NAD +

25. 26 26-25 © 2003 Thomson Learning, Inc. All rights reserved CA Cycle in Catabolism The catabolism of proteins, carbohydrates, and fatty acids all feed into the citric acid cycle at one or more points

26. 26 26-26 © 2003 Thomson Learning, Inc. All rights reserved Oxidative Phosphorylation Carried out by four closely related multisubunit membrane-bound complexes and two electron carriers, coenzyme Q and cytochrome c in a series of oxidation-reduction reactions, electrons from FADH 2 and NADH are transferred from one complex to the next until they reach O 2 O 2 is reduced to H 2 O as a result of electron transport, protons are pumped across the inner membrane to the intermembrane space

27. 26 26-27 © 2003 Thomson Learning, Inc. All rights reserved Complex I The sequence starts with complex I this large complex contains some 40 subunits, among them are a flavoprotein, several iron-sulfur (FeS) clusters, and coenzyme Q (CoQ, ubiquinone) complex I oxidizes NADH to NAD + the oxidizing agent is CoQ, which is reduced to CoQH 2 some of the energy released in this reaction is used to move 2H + from the matrix into the intermembrane space

28. 26 26-28 © 2003 Thomson Learning, Inc. All rights reserved Complex II complex II oxidizes FADH 2 to FAD the oxidizing agent is CoQ, which is reduced to CoQH 2 the energy released in this reaction is not sufficient to pump protons across the membrane

29. 26 26-29 © 2003 Thomson Learning, Inc. All rights reserved Complex III complex III delivers electrons from CoQH 2 to cytochrome c (Cyt c) this integral membrane complex contains 11 subunits, including cytochrome b, cytochrome c 1, and FeS clusters complex III has two channels through which the two H + from CoQH 2 are pumped from the matrix into the intermembrane space

30. 26 26-30 © 2003 Thomson Learning, Inc. All rights reserved Complex IV complex IV is also known as cytochrome oxidase it contains 13 subunits, one of which is cytochrome a 3 electrons flow from Cyt c (oxidized) in complex III to Cyt a 3 in complex IV from Cyt a 3 electrons are transferred to O 2 during this redox reaction, H + are pumped from the matrix into the intermembrane space Summing the reactions of complexes I - IV, six H + are pumped out per NADH and four H + per FADH 2

31. 26 26-31 © 2003 Thomson Learning, Inc. All rights reserved Coupling of Ox and Phos chemiosmotic theory To explain how electron and H + transport produce the chemical energy of ATP, Peter Mitchell proposed the chemiosmotic theory gradientthe energy-releasing oxidations give rise to proton pumping and a pH gradient across the inner mitochondrial membrane there is a higher concentration of H + in the intermembrane space than inside the mitochondrion proton translocating ATPasethis proton gradient provides the driving force to propel protons back into the mitochondrion through the enzyme complex called proton translocating ATPase

32. 26 26-32 © 2003 Thomson Learning, Inc. All rights reserved Coupling of Ox and Phos protons flow back into the matrix through channels in the F 0 unit of ATP synthase the flow of protons is accompanied by formation of ATP in the F 1 unit of ATP synthase The functions of oxygen are: to oxidize NADH to NAD + and FADH 2 to FAD so that these molecules can return to participate in the citric acid cycle provide energy for the conversion of ADP to ATP

33. 26 26-33 © 2003 Thomson Learning, Inc. All rights reserved Coupling of Ox and Phos The overall reactions of oxidative phosphorylation are:

34. 26 26-34 © 2003 Thomson Learning, Inc. All rights reserved The Energy Yield A portion of the energy released during electron transport is now built into ATP for each two-carbon acetyl unit entering the citric acid cycle, we get three NADH and one FADH 2 for each NADH oxidized to NAD +, we get three ATP for each FADH 2 oxidized to FAD, we get two ATP thus, the yield of ATP per two-carbon acetyl group oxidized to CO 2 is

35. 26 26-35 © 2003 Thomson Learning, Inc. All rights reserved Other Energy Forms The chemical energy of ATP is converted by the body to several other forms of energy Electrical energy Electrical energy the body maintains a K + concentration gradient across cell membranes; higher inside and lower outside it also maintains a Na + concentration gradient across cell membranes; lower inside, higher outside this pumping requires energy, which is supplied by the hydrolysis of ATP to ADP thus, the chemical energy of ATP is transformed into electrical energy, which operates in neurotransmission

36. 26 26-36 © 2003 Thomson Learning, Inc. All rights reserved Other Forms of Energy Mechanical energy Mechanical energy ATP drives the alternating association and dissociation of actin and myosin and, consequently, the contraction and relaxation of muscle tissue Heat energy Heat energy hydrolysis of ATP to ADP yields 7.3 kcal/mol some of this energy is released as heat to maintain body temperature

37. 26 26-37 © 2003 Thomson Learning, Inc. All rights reserved End Chapter 26 Bioenergetics