Fig. 9-1 Chapter 9 Cellular Respiration: Harvesting Chemical Energy

Cellular respiration includes both aerobic and anaerobic respiration but is often used to refer to aerobic respiration Although carbohydrates, fats, and proteins are all consumed as fuel, it is helpful to trace cellular respiration with the sugar glucose: C 6 H 12 O O 2  6 CO H 2 O + Energy (ATP + heat) – Redox Reactions

Fig. 9-UN4 Dehydrogenase Electrons from organic compounds are usually first transferred to NAD+, a coenzyme As an electron acceptor Each NADH (the reduced form of NAD+) represents stored energy that is tapped to synthesize ATP

Fig. 9-4 NAD + as an electron shuttle Dehydrogenase Reduction of NAD + Oxidation of NADH 2 e – + 2 H + 2 e – + H + NAD + + 2[H] NADH + H+H+ H+H+ Nicotinamide (oxidized form) Nicotinamide (reduced form) Nicotinamide adenine dinucleotide, a derivative of the vitamin niacin NADH passes the electrons to the electron transport chain

Fig. 9-2 Light energy ECOSYSTEM Photosynthesis in chloroplasts CO 2 + H 2 O Cellular respiration in mitochondria Organic molecules + O 2 ATP powers most cellular work Heat energy ATP

Fig. 9-5 Free energy, G (a) Uncontrolled reaction H2OH2O H / 2 O 2 Explosive release of heat and light energy (b) Cellular respiration Controlled release of energy for synthesis of ATP 2 H e – 2 H + 1 / 2 O 2 (from food via NADH) ATP 1 / 2 O 2 2 H + 2 e – Electron transport chain H2OH2O

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 Substrate-level phosphorylation ATP Cytosol Glucose Pyruvate I. Glycolysis Electrons carried via NADH Cellular respiration has three stages:

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 II.Citric acid cycle

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 III. 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 substrate-level phosphorylation – A smaller amount of ATP is formed in glycolysis and the citric acid cycle by ATP

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

Concept 9.2: Glycolysis harvests chemical energy by oxidizing glucose to pyruvate 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 ATP used 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

Fig Hexokinase ATP ADP 1 Phosphoglucoisomerase 2 Phosphogluco- isomerase 2 Glucose Glucose-6-phosphate Fructose-6-phosphate Glucose-6-phosphate Fructose-6-phosphate

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

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 Glyceraldehyde- 3-phosphate 4 5

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

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

Concept 9.3: The citric acid cycle completes the energy-yielding oxidation of organic molecules 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 The cycle oxidizes organic fuel derived from pyruvate, generating 1 ATP, 3 NADH, and 1 FADH2 per turn also called the Krebs cycle

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

Concept 9.4: During oxidative phosphorylation, chemiosmosis couples electron transport to ATP synthesis Following glycolysis and the citric acid cycle, NADH and FADH 2 account for most of the energy extracted from food These two electron carriers donate electrons to the electron transport chain, which powers ATP synthesis via oxidative phosphorylation

The Pathway of Electron Transport is in the cristae of the mitochondrion Most of the chain’s components are proteins, which exist in multiprotein complexes The carriers alternate reduced and oxidized states as they accept and donate electrons Electrons drop in free energy as they go down the chain and are finally passed to O 2, forming H 2 O

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 IV 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– prothetic groups of cytochromes

flavin nucleotides (tightly bound to flavoproteins) :

determining the sequence of electron carrier by inhibitors:

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 exergonic 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

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

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

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

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

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

What about NADH from glycolysis? NADH made in cytosol Can’t get into matrix of mitochondrion 2 mechanisms – In muscle and brain Glycerol phosphate shuttle – In liver and heart Malate / aspartate shuttle

glycerol-3-phosphate shuttle : (used in skeletal muscle and brain)  In muscle and brain  Each NADH converted to FADH2 inside mitochondrion  FADH2 enters later in the electron transport chain produces 1.5 ATP

Total ATP per glucose in muscle and brain Gycerol phosphate shuttle – 2 NADH per glucose -  2 FADH 2 – 2 FADH 2 X 1.5 ATP / FADH 2 ……….3.0 ATP – 2 ATP in glycoysis……………2.0 ATP – From pyruvate and Krebs 12.5 ATP X 2 per glucose … ATP Total = 30.0 ATP/ glucose

malate-aspartate shuttle : (used in liver, kidney and heart)

Malate – Aspartate Shuttle in cytosol In liver and heart NADH oxidized while reducing oxaloacetate to malate – Malated dehydrogenase Malate crosses membrane Malate – Aspartate Shuttle in matrix Malate reoxidized to oxaloacetate – Malate dehydrogenase – NAD + reduced to NADH NADH via electron transport yields 2.5 ATP

Total ATP per glucose in liver and heart Malate – Aspartate Shuttle – 2 NADH per glucose -  2 NADH – 2 NADH X 2.5 ATP / NADH…………5.0 ATP – 2 ATP from glycolysis………………..2.0 ATP – From pyruvate and Krebs 12.5 ATP X 2 per glucose …… ATP Total = 32.0 ATP/ glucose

Summary Total ATP / glucose – Muscle and brain30.0 ATP Uses glycerol phosphate shuttle – Heart and liver32.0 ATP Uses malate aspartate shuttle

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

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

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 Fermentation and Aerobic Respiration Compared Glycolysis probably evolved in ancient prokaryotes before there was oxygen in the atmosphere Gycolysis and the citric acid cycle are major intersections to various catabolic and anabolic pathways

The Versatility of Catabolism Catabolic pathways funnel electrons from many kinds of organic molecules into cellular respiration Glycolysis accepts a wide range of carbohydrates Proteins must be digested to amino acids; amino groups can feed glycolysis or the citric acid cycle Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig Proteins Carbohydrates Amino acids Sugars Fats GlycerolFatty acids Glycolysis Glucose Glyceraldehyde-3- Pyruvate P NH 3 Acetyl CoA Citric acid cycle Oxidative phosphorylation Biosynthesis (Anabolic Pathways) beta oxidation An oxidized gram of fat produces more than twice as much ATP as an oxidized gram of carbohydrate Catabolic pathways funnel electrons from many kinds of organic molecules into cellular respiration

Fig Glucose Glycolysis Fructose-6-phosphate Phosphofructokinase Fructose-1,6-bisphosphate Inhibits AMP Stimulates Inhibits Pyruvate Citrate Acetyl CoA Citric acid cycle Oxidative phosphorylation ATP + – – Regulation of Cellular Respiration via Feedback Mechanisms 1. Feedback inhibition is the most common mechanism for control 2. If ATP concentration begins to drop, respiration speeds up; when there is plenty of ATP, respiration slows down 3. Control of catabolism is based mainly on regulating the activity of enzymes at strategic points in the catabolic pathway

You should now be able to: 1.Name the three stages of cellular respiration; for each, state the region of the eukaryotic cell where it occurs and the products that result 2.In general terms, explain the role of the electron transport chain in cellular respiration 3.Explain where and how the respiratory electron transport chain creates a proton gradient