10/18/11 Chapter 9: Cellular Respiration

The Principle of Redox Chemical reactions that transfer electrons between reactants are called oxidation- reduction reactions, or redox reactions In oxidation, a substance loses electrons, or is oxidized In reduction, a substance gains electrons, or is reduced (the amount of positive charge is reduced)

Fig. 9-UN1 becomes oxidized (loses electron) becomes reduced (gains electron)

Redox Reactions: Oxidation and Reduction The transfer of electrons during chemical reactions releases energy stored in organic molecules This released energy is ultimately used to synthesize ATP

Oxidation of Organic Fuel Molecules During Cellular Respiration During cellular respiration, the fuel (such as glucose) is oxidized, and O 2 is reduced:

Fig. 9-UN3 becomes oxidized becomes reduced

Stepwise Energy Harvest via NAD + and the Electron Transport Chain In cellular respiration, glucose and other organic molecules are broken down in a series of steps Electrons from organic compounds are usually first transferred to NAD +, a coenzyme As an electron acceptor, NAD + functions as an oxidizing agent during cellular respiration Each NADH (the reduced form of NAD + ) represents stored energy that is tapped to synthesize ATP

NADH passes the electrons to the electron transport chain Unlike an uncontrolled reaction, the electron transport chain passes electrons in a series of steps instead of one explosive reaction O 2 pulls electrons down the chain in an energy-yielding tumble The energy yielded is used to regenerate ATP

The Stages of Cellular Respiration: A Preview Cellular respiration has three stages: –Glycolysis (breaks down glucose into two molecules of pyruvate) –The citric acid cycle (completes the breakdown of glucose) –Oxidative phosphorylation (accounts for most of the ATP synthesis)

Fig Mitochondrion Substrate-level phosphorylation ATP Cytosol Glucose Pyruvate Glycolysis Electrons carried via NADH Substrate-level phosphorylation ATP Electrons carried via NADH and FADH 2 Oxidative phosphorylation ATP Citric acid cycle Oxidative phosphorylation: electron transport and chemiosmosis

The process that generates most of the ATP is called oxidative phosphorylation because it is powered by redox reactions

Oxidative phosphorylation accounts for almost 90% of the ATP generated by cellular respiration A smaller amount of ATP is formed in glycolysis and the citric acid cycle by substrate-level phosphorylation

Fig. 9-7 Enzyme ADP P Substrate Enzyme ATP + Product

Glycolysis Glycolysis (“splitting of sugar”) breaks down glucose into two molecules of pyruvate Glycolysis occurs in the cytoplasm and has two major phases: –Energy investment phase –Energy payoff phase

Fig. 9-8 Energy investment phase Glucose 2 ADP + 2 P 2 ATPused formed 4 ATP Energy payoff phase 4 ADP + 4 P 2 NAD e – + 4 H + 2 NADH + 2 H + 2 Pyruvate + 2 H 2 O Glucose Net 4 ATP formed – 2 ATP used2 ATP 2 NAD e – + 4 H + 2 NADH + 2 H +

Fig ATP ADP Hexokinase 1 ATP ADP Hexokinase 1 Glucose Glucose-6-phosphate Glucose Glucose-6-phosphate Glucose enters the cell and is phosphoryla ted by hexokinase, which transfers a phosphate group to glucose

Fig Hexokinase ATP ADP 1 Phosphoglucoisomerase 2 Phosphogluco- isomerase 2 Glucose Glucose-6-phosphate Fructose-6-phosphate Glucose-6-phosphate Fructose-6-phosphate Glucose 6 phosphate is converted to its isomer fructose 6 phosphate by phosphogluc oisomerase

1 Fig Hexokinase ATP ADP Phosphoglucoisomerase Phosphofructokinase ATP ADP 2 3 ATP ADP Phosphofructo- kinase Fructose- 1, 6-bisphosphate Glucose Glucose-6-phosphate Fructose-6-phosphate Fructose- 1, 6-bisphosphate Fructose-6-phosphate 3 Phosphofruc tokinase transfers a phosphate group from ATP to the sugar investing another ATP, sugar is now ready to be split

Fig Glucose ATP ADP Hexokinase Glucose-6-phosphate Phosphoglucoisomerase Fructose-6-phosphate ATP ADP Phosphofructokinase Fructose- 1, 6-bisphosphate Aldolase Isomerase Dihydroxyacetone phosphate Glyceraldehyde- 3-phosphate Aldolase Isomerase Fructose- 1, 6- bisphosphate Dihydroxyacetone phosphate Glyceraldehyd e- 3-phosphate 4 5 Aldolase cleaves sugar into 2 3- carbon sugars

Fig NADH H + 2 P i 2 2 ADP 2 ATP This enzyme: 1.Oxidizes the sugar by transfer of electron s and H+ to NAD+ forming NADH 2.Exergon ic and enzyme uses energy to transfer phospha te to substrat e Fig NAD + NADH H + 2 2P i Triose phosphate dehydrogenase 1, 3-Bisphosphoglycerate 6 2 NAD + Glyceraldehyde- 3-phosphate Triose phosphate dehydrogenase NADH2 + 2 H + 2 P i 1, 3-Bisphosphoglycerate 6 2 2

Fig NAD + NADH 2 Triose phosphate dehydrogenase + 2 H + 2 P i 2 2 ADP 1, 3-Bisphosphoglycerate Phosphoglycerokinase 2 ATP 2 3-Phosphoglycerate ADP 2 ATP 1, 3-Bisphosphoglycerate 3-Phosphoglycerate Phosphoglycero- kinase 2 7 Glycolysis produces some ATP by substrate- level phophorylati on Total of 2 ATP because there are 2 sugar molecules

Fig Phosphoglycerate Triose phosphate dehydrogenase 2 NAD + 2 NADH + 2 H + 2 P i 2 2 ADP Phosphoglycerokinase 1, 3-Bisphosphoglycerate 2 ATP 3-Phosphoglycerate 2 Phosphoglyceromutase 2-Phosphoglycerate Phosphoglycero- mutase

Fig NAD + NADH H + Triose phosphate dehydrogenase 2 P i 1, 3-Bisphosphoglycerate Phosphoglycerokinase 2 ADP 2 ATP 3-Phosphoglycerate Phosphoglyceromutase Enolase 2-Phosphoglycerate 2 H 2 O Phosphoenolpyruvate Phosphoglycerate Enolase 2 2 H 2 O Phosphoenolpyruvate 9

Fig Triose phosphate dehydrogenase 2 NAD + NADH ADP 2 ATP Pyruvate Pyruvate kinase Phosphoenolpyruvate Enolase 2 H 2 O 2-Phosphoglycerate Phosphoglyceromutase 3-Phosphoglycerate Phosphoglycerokinase 2 ATP 2 ADP 1, 3-Bisphosphoglycerate + 2 H ADP 2 ATP Phosphoenolpyruvate Pyruvate kinase 2 Pyruvate 10 2 P i

If Oxygen is present… In the presence of O 2, pyruvate enters the mitochondrion Before the citric acid cycle can begin, pyruvate must be converted to acetyl CoA, which links the cycle to glycolysis

Fig CYTOSOLMITOCHONDRION NAD + NADH+ H Pyruvate Transport protein CO 2 Coenzyme A Acetyl CoA

Fig Pyruvate NAD + NADH + H + Acetyl CoA CO 2 CoA Citric acid cycle FADH 2 FAD CO NAD H + ADP +P i ATP NADH

Fig Acetyl CoA Oxaloacetate CoA—SH 1 Citrate Citric acid cycle

Fig Acetyl CoA Oxaloacetate Citrate CoA—SH Citric acid cycle 1 2 H2OH2O Isocitrate

Fig Acetyl CoA CoA—SH Oxaloacetate Citrate H2OH2O Citric acid cycle Isocitrate NAD + NADH + H +  -Keto- glutarate CO2CO2

Fig Acetyl CoA CoA—SH Oxaloacetate Citrate H2OH2O Isocitrate NAD + NADH + H + Citric acid cycle  -Keto- glutarate CoA—SH NAD + NADH + H + Succinyl CoA CO2CO2 CO2CO2

Fig Acetyl CoA CoA—SH Oxaloacetate Citrate H2OH2O Isocitrate NAD + NADH + H + CO2CO2 Citric acid cycle CoA—SH  -Keto- glutarate CO2CO2 NAD + NADH + H + Succinyl CoA CoA—SH GTP GDP ADP P i Succinate ATP

Fig Acetyl CoA CoA—SH Oxaloacetate H2OH2O Citrate Isocitrate NAD + NADH + H + CO2CO2 Citric acid cycle CoA—SH  -Keto- glutarate CO2CO2 NAD + NADH + H + CoA—SH P Succinyl CoA i GTP GDP ADP ATP Succinate FAD FADH 2 Fumarate

Fig Acetyl CoA CoA—SH Oxaloacetate Citrate H2OH2O Isocitrate NAD + NADH + H + CO2CO2  -Keto- glutarate CoA—SH NAD + NADH Succinyl CoA CoA—SH PP GDP GTP ADP ATP Succinate FAD FADH 2 Fumarate Citric acid cycle H2OH2O Malate i CO2CO2 + H + 3 4

Fig Acetyl CoA CoA—SH Citrate H2OH2O Isocitrate NAD + NADH + H + CO2CO2  -Keto- glutarate CoA—SH CO2CO2 NAD + NADH + H + Succinyl CoA CoA—SH P i GTP GDP ADP ATP Succinate FAD FADH 2 Fumarate Citric acid cycle H2OH2O Malate Oxaloacetate NADH +H + NAD

The Pathway of Electron Transport The electron transport chain is in the cristae of the mitochondrion Most of the chain’s components are proteins and multiprotein complexes Electrons release energy as they go down the chain and are finally passed to O 2, forming H 2 O Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig NADH NAD + 2 FADH 2 2 FAD Multiprotein complexes FAD FeS FMN FeS Q  Cyt b   Cyt c 1 Cyt c Cyt a Cyt a 3 IVIV Free energy (G) relative to O 2 (kcal/mol) (from NADH or FADH 2 ) 0 2 H / 2 O2O2 H2OH2O e–e– e–e– e–e–

Fig Protein complex of electron carriers H+H+ H+H+ H+H+ Cyt c Q    VV FADH 2 FAD NAD + NADH (carrying electrons from food) Electron transport chain 2 H / 2 O 2 H2OH2O ADP + P i Chemiosmosis Oxidative phosphorylation H+H+ H+H+ ATP synthase ATP 21 v=3y1dO4nNaKY

Electrons are transferred from NADH or FADH 2 to the electron transport chain Electrons are passed through a number of proteins including cytochromes to O 2 The electron transport chain generates no ATP Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Chemiosmosis: The Energy- Coupling Mechanism Electron transfer in the electron transport chain causes proteins to pump H + from the mitochondrial matrix to the intermembrane space H + then moves back across the membrane, passing through channels in ATP synthase ATP synthase uses the flow of H + to drive phosphorylation of ATP This is an example of chemiosmosis, the use of energy in a H + gradient to drive cellular work Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig INTERMEMBRANE SPACE Rotor H+H+ Stator Internal rod Cata- lytic knob ADP + P ATP i MITOCHONDRIAL MATRIX

The energy stored in a H + gradient across a membrane couples the redox reactions of the electron transport chain to ATP synthesis The H + gradient is referred to as a proton- motive force, emphasizing its capacity to do work Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

An Accounting of ATP Production by Cellular Respiration During cellular respiration, most energy flows in this sequence: glucose  NADH  electron transport chain  proton-motive force  ATP About 40% of the energy in a glucose molecule is transferred to ATP during cellular respiration, making about 38 ATP Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig Maximum per glucose: About 36 or 38 ATP + 2 ATP + about 32 or 34 ATP Oxidative phosphorylation: electron transport and chemiosmosis Citric acid cycle 2 Acetyl CoA Glycolysis Glucose 2 Pyruvate 2 NADH 6 NADH2 FADH 2 2 NADH CYTOSOL Electron shuttles span membrane or MITOCHONDRION

Concept 9.5: Fermentation and anaerobic respiration enable cells to produce ATP without the use of oxygen Most cellular respiration requires O 2 to produce ATP Glycolysis can produce ATP with or without O 2 (in aerobic or anaerobic conditions) In the absence of O 2, glycolysis couples with fermentation or anaerobic respiration to produce ATP Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

In alcohol fermentation, pyruvate is converted to ethanol in two steps, with the first releasing CO 2 Alcohol fermentation by yeast is used in brewing, winemaking, and baking Animation: Fermentation Overview Animation: Fermentation Overview Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 9-18a 2 ADP + 2 P i 2 ATP GlucoseGlycolysis 2 Pyruvate 2 NADH2 NAD H + CO 2 2 Acetaldehyde 2 Ethanol (a) Alcohol fermentation 2

Fig ADP + 2PiPi 2 ATP Glucose Glycolysis 2 NAD + 2 NADH 2 Pyruvate + 2 H + 2 Acetaldehyde 2 Ethanol (a) Alcohol fermentation 2 ADP + 2 PiPi 2 ATP GlucoseGlycolysis 2 NAD + 2 NADH + 2 H + 2 Pyruvate 2 Lactate (b) Lactic acid fermentation 2 CO 2

In lactic acid fermentation, pyruvate is reduced to NADH, forming lactate as an end product, with no release of CO 2 Lactic acid fermentation by some fungi and bacteria is used to make cheese and yogurt Human muscle cells use lactic acid fermentation to generate ATP when O 2 is scarce Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 9-18b Glucose 2 ADP + 2 P i 2 ATP Glycolysis 2 NAD + 2 NADH + 2 H + 2 Pyruvate 2 Lactate (b) Lactic acid fermentation

Obligate anaerobes carry out fermentation or anaerobic respiration and cannot survive in the presence of O 2 Yeast and many bacteria are facultative anaerobes, meaning that they can survive using either fermentation or cellular respiration In a facultative anaerobe, pyruvate is a fork in the metabolic road that leads to two alternative catabolic routes Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig Glucose Glycolysis Pyruvate CYTOSOL No O 2 present: Fermentation O 2 present: Aerobic cellular respiration MITOCHONDRION Acetyl CoA Ethanol or lactate Citric acid cycle