Chapter 9 Cellular Respiration

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

I. Catabolic Pathways and Production of ATP Fermentation = partial degradation of sugars that occurs without O 2 Aerobic respiration uses organic molecules and O 2 and yields ATP Anaerobic respiration = similar to aerobic but consumes compounds other than O 2

Cellular respiration includes aerobic and anaerobic C 6 H 12 O O 2  6 CO H 2 O + Energy (ATP + heat)

II. Redox Reactions: Oxidation and Reduction Transfer of electrons, releases energy stored in organic molecules, used to synthesize ATP

A. Principle of Redox Chemical reactions that transfer electrons between reactants are called oxidation-reduction reactions, or redox reactions Oxidation = substance loses electrons, oxidized Reduction = substance gains electrons, reduced (the amount of + charge is reduced) Electron donor = reducing agent Electron receptor = oxidizing agent

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

Fig. 9-UN2 becomes oxidized becomes reduced

Fig. 9-3 Reactants becomes oxidized becomes reduced Products Methane (reducing agent) Oxygen (oxidizing agent) Carbon dioxideWater

Fig. 9-UN3 becomes oxidized becomes reduced

B. NAD + and the Electron Transport Chain Glucose is broken down in a series of steps Electrons are first transferred to NAD +, a coenzyme As an electron acceptor, NAD + functions as an oxidizing agent Each NADH (the reduced form of NAD + ) represents stored energy that is tapped to make ATP How NAD works

Fig. 9-4 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)

NADH passes the electrons to the electron transport chain ETC 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 regenerates 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

III. Stages of Cellular Respiration: A Preview Cellular respiration has three stages: – Glycolysis (breaks down glucose into two molecules of pyruvate) – 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 Glycolysis Electrons carried via NADH

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 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 Oxidative phosphorylation: electron transport and chemiosmosis

Oxidative phosphorylation (powered by redox reactions) generates most of the ATP (about 90% of total from cellular resp) Other 10% 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

Concept 9.2: Glycolysis harvests chemical energy by oxidizing glucose to pyruvate Glycolysis (“splitting of sugar”) breaks down glucose into two molecules of pyruvate, 2 ATP and 2 NADH (high energy e - carriers) Glycolysis occurs in the cytoplasm and has two major phases: – Energy investment phase – Energy payoff phase How glycolysis works

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

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

IV. Citric acid cycle completes oxidation With O 2, pyruvate enters mitochondrion 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

Citric acid cycle (Krebs cycle) takes place within mito matrix Cycle oxidizes organic fuel derived from pyruvate, generating 1 ATP, 3 NADH, and 1 FADH 2 per turn (and 2 CO 2, cutting up “sugar” even more)

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 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

Overview Glycolysis - Citric Acid Cycle

V. Electron Transport Chain NADH and FADH 2 donate e - s to the electron transport chain, which powers ATP synthesis via oxidative phosphorylation In the cristae of mitochondrion Carriers alternate reduced and oxidized states as they accept and donate e - e - s drop in free energy as they go down the chain and are 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 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–

e - s are transferred from NADH or FADH 2 to the electron transport chain Electron transport chain generates no ATP Function is to break the large free-energy drop from food to O 2 into smaller steps that release energy in manageable amounts Electron Transport Chain and Oxi Phos (3min)

VI. Chemiosmosis: Energy-Coupling e - transfer in ETC causes proteins to pump H + from mito matrix to intermembrane space H + then moves back across membrane, passing through channels in ATP synthase ATP synthase uses the exergonic (energy releasing) flow of H + to drive phosphorylation of ATP (ADP to ATP) Chemiosmosis = use of energy in a H + gradient to drive cellular work H + gradient is a proton-motive force, emphasizing its capacity to do work

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

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

ETC / Oxi Phos Overview

VII. 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 energy in a glucose molecule is transferred to ATP during cellular respiration (about 36 / 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

Cell Respiration Part 2 (9min) Cellular Respiration Overview - Bozeman (14min)Cellular Respiration Overview - Bozeman (14min)

VIII. Fermentation and anaerobic respiration W/o O 2, glycolysis couples with fermentation or anaerobic respiration to produce ATP Anaerobic respiration uses an electron transport chain with an electron acceptor other than O 2, ex. sulfate Fermentation uses phosphorylation instead of an electron transport chain to generate ATP

IX. Types of Fermentation Fermentation = glycolysis plus reactions that regenerate NAD + (can be reused by glycolysis) Alcohol fermentation = pyruvate is converted to ethanol in two steps, w/ the first releasing CO 2 Yeast = used in brewing, winemaking, and baking

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

Lactic acid fermentation = pyruvate is reduced to NADH, forming lactate, w/ no release of CO 2 Some fungi and bacteria = cheese and yogurt Human muscle cells = generate ATP when O 2 is scarce

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

X. Fermentation and Aerobic Respiration Compared Both use glycolysis to oxidize glucose to pyruvate Have different final electron acceptors: an organic molecule (such as pyruvate or acetaldehyde) in fermentation and O 2 in cellular respiration Cellular respiration produces 38 ATP per glucose molecule; fermentation produces 2 ATP per glucose molecule

Obligate anaerobes = carry out fermentation or anaerobic respiration and cannot survive in the presence of O 2 Facultative anaerobes (Yeast and many bacteria) = can survive using either fermentation or cellular respiration – Pyruvate is a fork in the metabolic road that leads to two alternative catabolic routes

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

XI. Evolutionary Significance of Glycolysis Glycolysis occurs in nearly all organisms Glycolysis probably evolved in ancient prokaryotes before there was O 2 in atmosphere

XII. Versatility of Catabolism Catabolic pathways funnel electrons from many kinds of organic molecules into cellular respiration Glycolysis accepts a wide range of carbohydrates Proteins = digested to amino acids; amino groups can feed glycolysis / citric acid cycle

Fats = digested to glycerol (used in glycolysis) and fatty acids (used in generating acetyl CoA, by beta oxidation) An oxidized gram of fat produces more than 2xs as much ATP as an oxidized gram of carbohydrate

Fig Proteins Carbohydrates Amino acids Sugars Fats GlycerolFatty acids Glycolysis Glucose Glyceraldehyde-3- Pyruvate P NH 3 Acetyl CoA Citric acid cycle Oxidative phosphorylation

XIII. Regulation by Feedback Mechanisms Feedback inhibition is most common mechanism for control [ATP] begins to drop, resp speeds up; when ATP increases, resp slows down Control of catabolism is based on regulating the activity of enzymes at points in pathway

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 + – –