Chapter 9 Cellular Respiration

Living cells require transfusions of energy: From outside sources To perform their many tasks

powers most cellular work Energy Flows into an ecosystem as sunlight Leaves as heat Light energy ECOSYSTEM CO2 + H2O Photosynthesis in chloroplasts Cellular respiration in mitochondria Organic molecules + O2 ATP powers most cellular work Heat energy Figure 9.2

Catabolic Pathways and Production of ATP Yield energy by: Oxidizing organic fuels The breakdown of organic molecules is: Exergonic One catabolic process is called fermentation: It is a partial degradation of sugars It occurs without oxygen

Cellular respiration: The most prevalent and efficient catabolic pathway It consumes: Oxygen Organic molecules e.g. glucose It yields: ATP To keep working, cells must regenerate:

Redox Reactions: Oxidation and Reduction Catabolic pathways yield energy due to: Transfer of electrons Redox reactions involves: Transfer is from one reactant to another Results in both oxidation and reduction

In oxidation In reduction A substance loses electrons The substance is said to be oxidized In reduction A substance gains electrons The substance is said to be reduced

Examples of redox reactions Na + Cl Na+ + Cl– becomes oxidized (loses electron) becomes reduced (gains electron)

Oxidation of Organic Fuel Molecules During Cellular Respiration Glucose is oxidized and oxygen is reduced C6H12O6 + 6O2 6CO2 + 6H2O + Energy becomes oxidized becomes reduced

Stepwise Energy Harvest via NAD+ and the Electron Transport Chain Cellular respiration Oxidation of glucose in a series of steps Electrons from organic compounds are first: Transferred to NAD+, NAD+ (nicotineamide dinucleotide): is a coenzyme

Cellular Respiration Why carbohydrates and fat are high energy food? NAD+ H O O– P CH2 HO OH N+ C NH2 N Nicotinamide (oxidized form) + 2[H] (from food) Dehydrogenase Reduction of NAD+ Oxidation of NADH 2 e– + 2 H+ 2 e– + H+ NADH Nicotinamide (reduced form) Figure 9.4

NADH: Is the reduced form of NAD+ It passes the electrons to: The electron transport chain

(a) Uncontrolled reaction If electron transfer is not stepwise: A large release of energy occurs (explosion) (a) Uncontrolled reaction Free energy, G H2O Explosive release of heat and light energy Figure 9.5 A H2 + 1/2 O2

The electron transport chain: Passes electrons in a series of steps Passage is not in one explosive reaction Energy from the electron transfer is used to: Generate ATP

Electron transport chain (b) Cellular respiration (from food via NADH) 2 H+ + 2 e– 2 H+ 2 e– H2O Controlled release of energy for synthesis of ATP ATP Electron transport chain Free energy, G (b) Cellular respiration + Figure 9.5 B

The Stages of Cellular Respiration: A Preview Cellular respiration is: A cumulative function of three metabolic stages: Glycolysis The citric acid cycle Oxidative phosphorylation

Glycolysis means “splitting of sugar” It Occurs in the cytosol of the cell It harvests energy by oxidizing glucose to pyruvate Does not require oxygen Its end products: Two molecules of pyruvate Two ATP molecules Two NADH

Oxidative phosphorylation: electron transport and chemiosmosis An overview of cellular respiration Figure 9.6 Electrons carried via NADH Glycolsis Glucose Pyruvate ATP Substrate-level phosphorylation Electrons carried via NADH and FADH2 Citric acid cycle Oxidative phosphorylation: electron transport and chemiosmosis Oxidative Mitochondrion Cytosol

Both glycolysis and the citric acid cycle can generate ATP by: Substrate-level phosphorylation Figure 9.7 Enzyme ATP ADP Product Substrate P +

Energy investment phase Glycolysis consists of two major phases Energy investment phase Energy payoff phase A total of 4 ATP molecules are produced Two ATP molecules are used The net number of ATP molecules is two Glycolysis Citric acid cycle Oxidative phosphorylation ATP 2 ATP 4 ATP used formed Glucose 2 ATP + 2 P 4 ADP + 4 2 NAD+ + 4 e- + 4 H + 2 NADH + 2 H+ 2 Pyruvate + 2 H2O Energy investment phase Energy payoff phase 4 ATP formed – 2 ATP used 2 NAD+ + 4 e– + 4 H + Figure 9.8

Phosphoglucoisomerase A closer look at the energy investment phase Dihydroxyacetone phosphate Glyceraldehyde- 3-phosphate H OH HO CH2OH O P CH2O CH2 C CHOH ATP ADP Hexokinase Glucose Glucose-6-phosphate Fructose-6-phosphate Phosphoglucoisomerase Phosphofructokinase Fructose- 1, 6-bisphosphate Aldolase Isomerase Glycolysis 1 2 3 4 5 Oxidative phosphorylation Citric acid cycle Figure 9.9 A

1, 3-Bisphosphoglycerate A closer look at the energy payoff phase 2 NAD+ NADH 2 + 2 H+ Triose phosphate dehydrogenase P i P C CHOH O CH2 O– 1, 3-Bisphosphoglycerate 2 ADP 2 ATP Phosphoglycerokinase 3-Phosphoglycerate Phosphoglyceromutase CH2OH H 2-Phosphoglycerate 2 H2O Enolase Phosphoenolpyruvate Pyruvate kinase CH3 6 8 7 9 10 Pyruvate Figure 9.8 B

Takes place in the matrix of the mitochondrion Requires oxygen The Citric Acid Cycle Takes place in the matrix of the mitochondrion Requires oxygen At the end of the cycle: Glucose breakdown is completed All the original carbon in the original glucose molecule has been lost as CO2 The two acetyl CoA that entered the cycle produce a total of: Two ATP (by substrate level phosphorylation) Six NADH Two FADH2

Before the citric acid cycle can begin Pyruvate must first be converted “oxidized” to: Acetyl CoA Acetyl CoA links the cycle to glycolysis CYTOSOL MITOCHONDRION NADH + H+ NAD+ 2 3 1 CO2 Coenzyme A Pyruvate Acetyle CoA S CoA C CH3 O Transport protein O– Figure 9.10

Oxidative phosphorylation An overview of the citric acid cycle ATP 2 CO2 3 NAD+ 3 NADH + 3 H+ ADP + P i FAD FADH2 Citric acid cycle CoA Acetyle CoA NADH CO2 Pyruvate (from glycolysis, 2 molecules per glucose) Glycolysis Oxidative phosphorylation Figure 9.11

A closer look at the citric acid cycle Acetyl CoA NADH Oxaloacetate Citrate Malate Fumarate Succinate Succinyl CoA a-Ketoglutarate Isocitrate Citric acid cycle S SH FADH2 FAD GTP GDP NAD+ ADP P i CO2 H2O + H+ C CH3 O COO– CH2 HO HC CH 1 2 3 4 5 6 7 8 Glycolysis Oxidative phosphorylation ATP Figure 9.12 Figure 9.12

Oxidative Phosphorylation Driven by the electron transport chain Electrons (generated during glycolys & citric acid cycle) are escorted & donated by: NaDH FADH2 Released energy during electron transfer is used thru chemiosmosis to generates ATP

The Pathway of Electron Transport In the electron transport chain Electrons from NADH and FADH2 lose energy in several steps At the end of the chain Electrons are passed to oxygen, forming water H2O O2 NADH FADH2 FMN Fe•S O FAD Cyt b Cyt c1 Cyt c Cyt a Cyt a3 2 H + + 12 I II III IV Multiprotein complexes 10 20 30 40 50 Free energy (G) relative to O2 (kcl/mol) Figure 9.13

Chemiosmosis Is an energy-coupling mechanism It uses energy in the form of a H+ gradient across a membrane to drive ATP synhesis

Chemiosmosis: The Energy-Coupling Mechanism ATP synthase Is the enzyme that actually makes ATP INTERMEMBRANE SPACE H+ P i + ADP ATP A rotor within the membrane spins clockwise when H+ flows past it down the H+ gradient. A stator anchored in the membrane holds the knob stationary. A rod (for “stalk”) extending into the knob also spins, activating catalytic sites in the knob. Three catalytic sites in the stationary knob join inorganic Phosphate to ADP to make ATP. MITOCHONDRIAL MATRIX Figure 9.14

Figure 9.15 ATP synthase Protein complex of electron carriers Cyt c IV Q III I II 2 H+ + ½ O2 H2O FADH2 FAD NADH NAD+ Figure 9.15 Chemiosmosis couples the electron transport chain to ATP synthesis ADP + P ATP i (carrying electrons from food) H+ Electron transport chain Chemiosmosis 1 2 Oxidative phosphorylation

Figure 9.15a 1 H+ H+ H+ Cyt c Cyt c IV Q III I II 2 H+ + ½ O2 H2O FAD Protein complex of electron carriers H+ Cyt c Cyt c IV Q III I II 2 H+ + ½ O2 H2O FADH2 FAD Figure 9.15a Chemiosmosis couples the electron transport chain to ATP synthesis (part 1: electron transport chain) NAD+ NADH (carrying electrons from food) 1 Electron transport chain

Figure 9.15b 2 H+ ADP + ATP H+ P ATP synthase i Chemiosmosis Figure 9.15b Chemiosmosis couples the electron transport chain to ATP synthesis (part 2: chemiosmosis) ADP + P ATP i H+ Chemiosmosis 2

Figure 9.14 INTERMEMBRANE SPACE Stator H+ Rotor Internal rod Catalytic knob Figure 9.14 ATP synthase, a molecular mill ADP + P i ATP MITOCHONDRIAL MATRIX

At certain steps along the electron transport chain: Chemiosmosis At certain steps along the electron transport chain: The electron transfer causes protein complexes to pump H+ Hydrogrn ions (H+) are pumped from the mitochondrial matrix to the intermembrane space This creates a H+ gradient (stored energy) that drives ATP synthase to make ATP from: ADP, and inorganic phosphate

Electron transport chain Oxidative phosphorylation Chemiosmosis and the electron transport chain Oxidative phosphorylation. electron transport and chemiosmosis Glycolysis ATP Inner Mitochondrial membrane H+ P i Protein complex of electron carners Cyt c I II III IV (Carrying electrons from, food) NADH+ FADH2 NAD+ FAD+ 2 H+ + 1/2 O2 H2O ADP + Electron transport chain Electron transport and pumping of protons (H+), which create an H+ gradient across the membrane Chemiosmosis ATP synthesis powered by the flow Of H+ back across the membrane synthase Q Oxidative phosphorylation Intermembrane space mitochondrial matrix Figure 9.15

An Accounting of ATP Production by Cellular Respiration During respiration, most energy flows in this sequence: Glucose NADH electron transport chain proton-motive force ATP

There are three main processes in this metabolic enterprise Electron shuttles span membrane CYTOSOL 2 NADH 2 FADH2 6 NADH Glycolysis Glucose 2 Pyruvate Acetyl CoA Citric acid cycle Oxidative phosphorylation: electron transport and chemiosmosis MITOCHONDRION by substrate-level phosphorylation by oxidative phosphorylation, depending on which shuttle transports electrons from NADH in cytosol Maximum per glucose: About 36 or 38 ATP + 2 ATP + about 32 or 34 ATP or Figure 9.16

During cellular respiration: About 40% of the energy in a glucose molecule is transferred to ATP This result in making 36-38 ATP: 2 (net) ATP (from glycolysis, by substrate- level phosphorylation) 2 ATP (from citric acid cycle; by substrate- level phosphorylation) 32-34 ATP (from electron transfer chain; by oxidative phosphorylation

In the absence of oxygen: Fermentation Fermentation: Enables some cells to produce ATP without the use of oxygen Cellular respiration Relies on oxygen to produce ATP In the absence of oxygen: Cells can still produce ATP through a process called fermentation

Glycolysis vs Fermentation Can produce ATP in the presence or absence of oxygen, i.e. in aerobic or anaerobic conditions

Types of Fermentation Fermentation: Types: Consists of: Glycolysis, plus reactions that regenerate NAD+, which can be reused by glyocolysis Types: Alcohol fermentation: Pyruvate is converted (in two steps): 1st to acetaldehyde and CO2 Then, to ethanol Lactic acid fermentation: Pyruvate is reduced directly to NADH to form lactate as a waste product

(a) Alcohol fermentation (b) Lactic acid fermentation Types of Fermentation 2 ADP + 2 P1 2 ATP Glycolysis Glucose 2 NAD+ 2 NADH 2 Pyruvate 2 Acetaldehyde 2 Ethanol (a) Alcohol fermentation 2 Lactate (b) Lactic acid fermentation H OH CH3 C O – O O– CO2 2 Figure 9.17

Fermentation and Cellular Respiration Compared Both use glycolysis to oxidize glucose and other organic fuels to pyruvate Both differ in their final electron acceptor Cellular respiration produces more ATP

Pyruvate is a key juncture in catabolism Glucose CYTOSOL Pyruvate No O2 present Fermentation O2 present Cellular respiration Ethanol or lactate Acetyl CoA MITOCHONDRION Citric acid cycle Figure 9.18

The Versatility of Catabolism Glycolysis and the citric acid cycle connect to many other metabolic pathways Catabolic pathways Funnel electrons from many kinds of organic molecules into cellular respiration

The catabolism of various molecules from food Amino acids Sugars Glycerol Fatty Glycolysis Glucose Glyceraldehyde-3- P Pyruvate Acetyl CoA NH3 Citric acid cycle Oxidative phosphorylation Fats Proteins Carbohydrates Figure 9.19

Biosynthesis (Anabolic Pathways) The body Uses small molecules to build other substances These small molecules may come: Directly from food, Through: Glycolysis The citric acid cycle

Regulation of Cellular Respiration via Feedback Mechanisms Is controlled by allosteric enzymes at key points in glycolysis and the citric acid cycle

Fructose-1,6-bisphosphate The control of cellular respiration Glucose Glycolysis Fructose-6-phosphate Phosphofructokinase Fructose-1,6-bisphosphate Inhibits Pyruvate ATP Acetyl CoA Citric acid cycle Citrate Oxidative phosphorylation Stimulates AMP + – Figure 9.20