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Chapter 9. Cellular Respiration: Harvesting Chemical Energy. Life is Work. Living cells Require transfusions of energy from outside sources to perform their many tasks Ultimate energy source is SUN. Figure 9.1. The giant panda Obtains energy for its cells by eating plants. Light energy.
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Chapter 9 Cellular Respiration: Harvesting Chemical Energy
Life is Work Living cells • Require transfusions of energy from outside sources to perform their many tasks • Ultimate energy source is SUN
Figure 9.1 • The giant panda • Obtains energy for its cells by eating plants
Light energy ECOSYSTEM Photosynthesisin chloroplasts Organicmolecules CO2 + H2O + O2 Cellular respirationin mitochondria ATP powers most cellular work Heatenergy Figure 9.2 • Energy • Flows into an ecosystem as sunlight and leaves as heat
Catabolic Pathways Catabolic is the breakdown of molecules Ex. Cellular respiration breaks down glucose & releases energy Yields ATP exergonic reaction (-686 kcal/mol) *Does not directly move or pump anything or do other cellular work
How does a catabolic pathway yield energy? *By transferring electrons during chemical reaction. Relocation of electrons release energy stored in the bonds of organic molecules. Uses the principle of REDOX reactions
The Principle of Redox • Redox reactions terms 1. Oxidation (LEO) 2. Reduction (GER) 3. Reducing agent (electron donor) 4. Oxidizing agent (electron acceptor)
becomes oxidized(loses electron) Na + Cl Na+ + Cl– becomes reduced(gains electron) • Examples of redox reactions
Products Reactants becomes oxidized + + + Energy 2O2 CO2 2 H2O CH4 becomes reduced H C C O O O O H O H H H H Oxygen(oxidizingagent) Methane(reducingagent) Carbon dioxide Water Figure 9.3 • Some redox reactions • Do not completely exchange electrons • Change the degree of electron sharing in covalent bonds
becomes oxidized C6H12O6 + 6O2 6CO2 + 6H2O + Energy becomes reduced Oxidation of Organic Fuel Molecules During Cellular Respiration • During cellular respiration • Glucose is oxidized and oxygen is reduced
Cellular respiration Oxidizes glucose in a series of steps Catalyzed by ENZYMES Electrons travel with hydrogen atom
2 e– + 2 H+ 2 e– + H+ NAD+ NADH H Dehydrogenase O O H H Reduction of NAD+ + + 2[H] C NH2 NH2 C (from food) Oxidation of NADH N N+ Nicotinamide(reduced form) Nicotinamide(oxidized form) CH2 O O O O– P O H H OH O O– HO P NH2 HO CH2 O N N H N H N O H H HO OH Figure 9.4 • Electrons from organic compounds • Are usually first transferred to NAD+, a coenzyme
NADH, the reduced form of NAD+ • Passes the electrons to the electron transport chain • Oxygen is FINAL ELECTRON ACCEPTOR • * electrons go downhill (think hill, higher up has more PE)
H2 + 1/2 O2 Explosiverelease ofheat and lightenergy (a) Uncontrolled reaction Free energy, G Figure 9.5 A H2O • If electron transfer is not stepwise • A large release of energy occurs • As in the reaction of hydrogen and oxygen to form water
The electron transport chain (ETS) • Passes electrons in a series of steps instead of in one explosive reaction • NADH used in ETS • Uses the energy from the electron transfer to form ATP
2 H + 1/2 O2 (from food via NADH) Controlled release of energy for synthesis ofATP 2 H+ + 2 e– ATP ATP Free energy, G Electron transport chain ATP 2 e– 1/2 O2 2 H+ H2O Figure 9.5 B (b) Cellular respiration
The Stages of Cellular Respiration: A Preview • Respiration is a cumulative function of three metabolic stages 1. Glycolysis (technically not respiration, but is included b/c it’s the first step whether oxygen is present or not) 2. The citric acid cycle 3. Oxidative phosphorylation
1. Glycolysis (occurs in cytoplasm) • Breaks down glucose into two molecules of pyruvate 2. The citric acid cycle (mitochrondrial matrix) • Completes the breakdown of glucose
3. Oxidative phosphorylation (occurs in the inner mitochondria membrane) a. Is driven by the electron transport chain b. chemiosmosis • Generates ATP – 90% of all ATP cell makes
Electrons carried via NADH and FADH2 Electrons carried via NADH Oxidativephosphorylation:electron transport andchemiosmosis Citric acid cycle Glycolsis Pyruvate Glucose Cytosol Mitochondrion ATP ATP ATP Substrate-level phosphorylation Oxidative phosphorylation Substrate-level phosphorylation Figure 9.6 • An overview of cellular respiration
Enzyme Enzyme ADP P Substrate + ATP Product Figure 9.7 • Both glycolysis and the citric acid cycle • Can generate ATP by substrate-level phosphorylation
Stages of Cellular Respiration 1. Glycolysis harvests energy by oxidizing glucose to pyruvate • Glycolysis • Means “splitting of sugar” • Breaks down glucose into pyruvate • Occurs in the cytoplasm of the cell
Glycolysis Oxidativephosphorylation Citricacidcycle ATP ATP ATP Energy investment phase Glucose P 2 ATP + 2 used 2 ATP Energy payoff phase formed P 4 ATP 4 ADP + 4 2 NAD+ + 4 e- + 4 H + + 2 H+ 2 NADH 2 Pyruvate + 2 H2O Glucose 2 Pyruvate + 2 H2O 4 ATP formed – 2 ATP used 2 ATP + 2 H+ 2 NADH 2 NAD+ + 4 e– + 4 H + Figure 9.8 • Glycolysis consists of two major phases • A. Energy investment phase • B. Energy payoff phase
A. Energy Investment phase Steps 1. Glu glu-6-phospate Hexokinase adds P group ATP used • glu-6-P fructose-6-P (isomer) Phosphoglucoisomerase • fru-6-P fru 1,6 bisphosphate Phosphofructokinase adds P group ATP used
Fru 1,6 bisP dihydroxyacetone or glyceraldehyde-3-P Aldolase splits into 2 3-C groups (ISOMERS) • ISOMERASE catalyzes rxn btwn two forms Equilibrium never met b/c next step only uses glyceraldehyde-3-P
CH2OH Citric acid cycle H H Oxidative phosphorylation H Glycolysis H HO HO OH H OH Glucose 1 2 3 5 4 ATP Hexokinase ADP CH2OH P O H H H H OH HO H OH Glucose-6-phosphate Phosphoglucoisomerase CH2O P O CH2OH H HO HO H H HO Fructose-6-phosphate ATP Phosphofructokinase ADP CH2 O O CH2 P P O HO H OH H HO Fructose- 1, 6-bisphosphate Aldolase H O CH2 P Isomerase C O O C CHOH CH2OH O CH2 P Dihydroxyacetone phosphate Glyceraldehyde- 3-phosphate Figure 9.9 A
B. Energy Payoff Phase • Glyceraldehyde-3-P 1,3-biphosphoglycerate Transfer of electrons & H+ to NAD+ Forms 2 NADH Triose phosphate dehydrogenase • 1,3-biphosphoglycerate 3-phosphoglycerate Phosphoglycerokinase 2 ATP produced
8. 3-Phosphoglycerate 2-Phosphoglycerate • Relocates the P group • Phosphoglyceromutase • 2-Phosphoglycerate phosphoenolpyruvate (PEP) Enolase 2 water molecules released Molecule has unstable P bond
10. Phosphoenolpyruvate PYRUVATE P group goes to ADP Pyruvate kinase 2 ATP formed Sum of Glycolysis 2 net ATP 2 NADH 2 pyruvate
2 NAD+ Triose phosphate dehydrogenase P i 2 2 NADH + 2 H+ 10 7 9 8 6 2 O C O P CHOH P CH2 O 1, 3-Bisphosphoglycerate 2 ADP Phosphoglycerokinase 2 ATP O– 2 C CHOH O P CH2 3-Phosphoglycerate Phosphoglyceromutase O– 2 C O P C H O CH2OH 2-Phosphoglycerate Enolase 2 H2O O– 2 C O P C O CH2 Phosphoenolpyruvate 2 ADP Pyruvate kinase 2 ATP O– 2 C O C O CH3 Figure 9.8 B Pyruvate
Stages of Cellular Respiration • The citric acid cycle (Kreb’s cycle) if oxygen present pryuvate enters the matrix of the mitochondrion A. Btwn glycolysis & Krebs: Pyruvate Acetyl CoA • Carbon dioxide given off • NADH is formed • CoA added to pyruvate
CYTOSOL MITOCHONDRION + H+ NAD+ NADH O– CoA S 2 C O C O C O CH3 1 3 CH3 Acetyle CoA Pyruvate CO2 Coenzyme A Transport protein Figure 9.10 • Before the citric acid cycle can begin • Pyruvate must first be converted to acetyl CoA, which links the cycle to glycolysis
Pyruvate(from glycolysis,2 molecules per glucose) Oxidativephosphorylation Glycolysis Citricacidcycle ATP ATP ATP CO2 CoA NADH + 3 H+ Acetyle CoA CoA CoA Citricacidcycle 2 CO2 3 NAD+ FADH2 FAD 3 NADH + 3 H+ ADP + Pi ATP Figure 9.11 • An overview of the citric acid cycle
Citric Acid Cycle • Acetyl CoA enters Krebs cycle 8 steps 1. Acetyl CoA adds to oxaloacetate citrate 2. Citrate Isocitrate (one water removed, one water added) 3. Isocitrate alpha- ketoglutarate Carbon dioxide given off NADH formed
Alpha-ketoglutarate Succinyl CoA NADH formed Carbon dioxide given off • Succinyl CoA Succinate ATP formed • Succinate Fumarate FADH2 formed • Fumarate Malate Water added
8. Malate Oxaloacetate • NADH formed TOTAL per pyruvate (MULTIPLY BY 2 to get total) Before enter Kreb’s cycle: 1 NADH CO2 produced Krebs cycle: 2 CO2 1 ATP 3 NADH FADH2
Citric acid cycle Oxidative phosphorylation Glycolysis S CoA C O CH3 Acetyl CoA CoA SH H2O O C COO– NADH 1 COO– CH2 + H+ COO– CH2 COO– NAD+ Oxaloacetate 8 C COO– HO CH2 2 CH2 HC COO– COO– COO– HO CH HO CH Malate Citrate COO– CH2 Isocitrate COO– CO2 Citric acid cycle 3 H2O 7 NAD+ COO– NADH COO– CH + H+ Fumarate CH2 CoA SH HC a-Ketoglutarate CH2 COO– C O 4 6 SH CoA COO– COO– COO– CH2 5 CH2 FADH2 CO2 CH2 CH2 NAD+ FAD C O COO– Succinate NADH CoA S P i + H+ Succinyl CoA GDP GTP ADP ATP Figure 9.12 Figure 9.12
Oxidative Phosphorylation • Chemiosmosis couples electron transport to ATP synthesis • NADH and FADH2 • Donate electrons to the electron transport chain, which then powers ATP synthesis • ATP is not produced directly
A. Electron Transport Chain • Electrons from NADH and FADH2 lose energy in several steps • Located in the folds of inner membrane called CRISTAE • In the cristae, protein complexes I- IV electrons are transferred • Cytochromes – proteins that are electron carriers w/in complexes Electron acceptor – O2 (form H2O)
NADH 50 FADH2 Multiproteincomplexes I 40 FAD FMN II Fe•S Fe•S O III Cyt b 30 Fe•S Cyt c1 IV Free energy (G) relative to O2 (kcl/mol) Cyt c Cyt a Cyt a3 20 10 0 O2 2 H + + 12 Figure 9.13 H2O • 1. At complex I, NADH adds e- at higher level 2. FADH2 at complex II (1/3 less energy for ATP)
A rotor within the membrane spins clockwise whenH+ flows past it down the H+ gradient. INTERMEMBRANE SPACE H+ H+ H+ H+ H+ H+ H+ A stator anchoredin the membraneholds the knobstationary. A rod (for “stalk”)extending into the knob alsospins, activatingcatalytic sites inthe knob. H+ Three catalytic sites in the stationary knobjoin inorganic Phosphate to ADPto make ATP. ADP + ATP P i MITOCHONDRIAL MATRIX Figure 9.14 B. Chemiosmosis: The Energy-Coupling Mechanism • ATP synthase (enzyme that actually makes ATP) • Like an ion pump in reverse
At certain steps along the electron transport chain 1. Electron transfer causes protein complexes I-IV to pump H+ from the mitochondrial matrix to the intermembrane space
2. The resulting H+ gradient A. Stores energy B. Drives chemiosmosis in ATP synthase C. Is referred to as a proton-motive force
Chemiosmosis Is an energy-coupling mechanism that uses energy in the form of a H+ gradient across a membrane to drive cellular work
Inner Mitochondrial membrane Oxidative phosphorylation. electron transport and chemiosmosis Glycolysis ATP ATP ATP H+ H+ H+ H+ Cyt c Protein complex of electron carners Intermembrane space Q IV I III ATP synthase Inner mitochondrial membrane II H2O FADH2 2 H+ + 1/2 O2 FAD+ NADH+ NAD+ ATP ADP + P i (Carrying electrons from, food) H+ Mitochondrial matrix Chemiosmosis ATP synthesis powered by the flow Of H+ back across the membrane Electron transport chain Electron transport and pumping of protons (H+), which create an H+ gradient across the membrane Figure 9.15 Oxidative phosphorylation • Chemiosmosis and the electron transport chain
ATP Production Total Overall: Glu NADH ETS Promotive force ATP Glycolysis total: Citric Acid (2 turns): Ox Phos: 2 ATP 2 ATP 2 NADH 6 NADH 30 ATP 2 pyruvate 2 FADH2 4 ATP 2 NADH (before cycle) Total: 34 ATP
ATP Production TOTAL (glycolysis, Kreb’s cycle, ox phos) 34 ATP (from ox phos) 4 ATP (substrate phos) • 2 ATP (active transport, using FADH instead of NADH before entering Kreb’s cycle) TOTAL: net 36 ATP OVERALL
Electron shuttles span membrane MITOCHONDRION CYTOSOL 2 NADH or 2 FADH2 2 FADH2 2 NADH 2 NADH 6 NADH Glycolysis Oxidative phosphorylation: electron transport and chemiosmosis Citric acid cycle 2 Acetyl CoA 2 Pyruvate Glucose + 2 ATP + 2 ATP + about 32 or 34 ATP by oxidative phosphorylation, depending on which shuttle transports electrons from NADH in cytosol by substrate-level phosphorylation by substrate-level phosphorylation About 36 or 38 ATP Maximum per glucose: Figure 9.16 • There are three main processes in this metabolic enterprise
Fermentation (lack of oxygen) Cellular respiration Relies on oxygen to produce ATP In the absence of oxygen • Cells can still produce ATP through fermentation
Glycolysis • Can produce ATP with or without oxygen, in aerobic or anaerobic conditions • Couples with fermentation to produce ATP