Overview: The Energy of Life The living cell Chapter 8 Overview: The Energy of Life The living cell Is a miniature factory where thousands of reactions occur Converts energy in many ways Figure 8.1

Metabolism Is the totality of an organism’s chemical reactions Arises from interactions between molecules Metabolism= Catabolism + Anabolism

The system is at equilibrium At maximum stability The system is at equilibrium Not Stable Chemical reaction. In a cell, a sugar molecule is broken down into simpler molecules. . Diffusion. Molecules in a drop of dye diffuse until they are randomly dispersed. Gravitational motion. Objects move spontaneously from a higher altitude to a lower one. More free energy (higher G) Less stable Greater work capacity Less free energy (lower G) More stable Less work capacity In a spontaneously change The free energy of the system decreases (∆G<0) The system becomes more stable The released free energy can be harnessed to do work (a) (b) (c) Figure 8.5  Yeah! More STABLE

An analogy for cellular respiration Not stable Figure 8.7 (c) A multistep open hydroelectric system. Cellular respiration is analogous to this system: Glucose is broken down in a series of exergonic reactions that power the work of the cell. The product of each reaction becomes the reactant for the next, so no reaction reaches equilibrium. ∆G < 0 Stable

The Structure and Hydrolysis of ATP ATP (adenosine triphosphate) Is the cell’s energy shuttle Provides energy for cellular functions Figure 8.8 O CH2 H OH N C HC NH2 Adenine Ribose Phosphate groups - CH

Energy is released from ATP When the terminal phosphate bond is broken Figure 8.9 P Adenosine triphosphate (ATP) H2O + Energy Inorganic phosphate Adenosine diphosphate (ADP) P i

Can be coupled to other reactions ATP hydrolysis Can be coupled to other reactions Endergonic reaction: ∆G is positive, reaction is not spontaneous ∆G = +3.4 kcal/mol Glu ∆G = + 7.3 kcal/mol ATP H2O + NH3 ADP NH2 Glutamic acid Ammonia Glutamine Exergonic reaction: ∆ G is negative, reaction is spontaneous P Coupled reactions: Overall ∆G is negative; together, reactions are spontaneous ∆G = –3.9 kcal/mol Figure 8.10

The three types of cellular work Are powered by the hydrolysis of ATP (c) Chemical work: ATP phosphorylates key reactants P Membrane protein Motor protein P i Protein moved (a) Mechanical work: ATP phosphorylates motor proteins ATP (b) Transport work: ATP phosphorylates transport proteins Solute transported Glu NH3 NH2 + Reactants: Glutamic acid and ammonia Product (glutamine) made ADP Figure 8.11

Organization of the Chemistry of Life into Metabolic Pathways A metabolic pathway has many steps That begin with a specific molecule and end with a product That are each catalyzed by a specific enzyme Enzyme 1 Enzyme 2 Enzyme 3 A B C D Reaction 1 Reaction 2 Reaction 3 Starting molecule Product

Catabolic pathways Break down complex molecules into simpler compounds Exergonic reaction - Release energy

Anabolic pathways Build complicated molecules from simpler ones Consume energy

Forms of Energy Energy Is the capacity to cause change Exists in various forms, of which some can perform work

Kinetic energy Potential energy Is the energy associated with motion Is stored in the location of matter Includes chemical energy stored in molecular structure

Chapter 9 Cellular Respiration: Harvesting Chemical Energy

Overview: Life Is Work Living cells Require transfusions of energy from outside sources to perform their many tasks

The giant panda Obtains energy for its cells by eating plants Figure 9.1

powers most cellular work Energy Flows into an ecosystem as sunlight and 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

Concept 9.1: Catabolic pathways yield energy by oxidizing organic fuels

Catabolic Pathways and Production of ATP The breakdown of organic molecules is exergonic- releases energy

One catabolic process, fermentation Is a partial degradation of sugars that occurs without oxygen

Cellular respiration Is the most prevalent and efficient catabolic pathway Consumes oxygen and organic molecules such as glucose Yields ATP

Redox Reactions: Oxidation and Reduction Catabolic pathways yield energy Due to the transfer of electrons from high potential energy (i.e. in animal cell from Glucose) to Low potential energy (electron acceptor usually an electron carrier, but ultimately delivered to oxygen in the mitochondria)

The Principle of Redox Redox reactions Transfer electrons from one reactant to another by oxidation and reduction

In oxidation In reduction A substance loses electrons, or is oxidized A substance gains electrons, or is 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 Oxidizes glucose in a series of steps

Electrons from organic compounds Are usually first transferred to NAD+, a coenzyme- electron carrier 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, the reduced form of NAD+ Passes the electrons to the electron transport chain or system (ETC also known as the ETS) in the Mitochondria Intermembrane space MATRIX

(a) Uncontrolled reaction If electron transfer is not stepwise A large release of energy occurs As in the reaction of hydrogen and oxygen to form water (a) Uncontrolled reaction Free energy, G H2O Explosive release of heat and light energy Figure 9.5 A H2 + 1/2 O2

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 Respiration is a cumulative function of three metabolic stages Glycolysis The citric acid cycle Oxidative phosphorylation

Glycolysis The citric acid cycle Breaks down glucose into two molecules of pyruvate The citric acid cycle Completes the breakdown of glucose

Oxidative phosphorylation Is driven by the electron transport chain that occurs in the Mitochondria Generates ATP

A animal cell

Mitochondria are enclosed by two membranes A smooth outer membrane An inner membrane folded into cristae Mitochondrion Intermembrane space Outer membrane Free ribosomes in the mitochondrial matrix Mitochondrial DNA Inner Cristae Matrix 100 µm Figure 6.17

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 +

Concept 9.2: Glycolysis harvests energy by oxidizing glucose to pyruvate Means “splitting of sugar” Breaks down glucose into pyruvate Occurs in the cytoplasm of the cell

Energy investment phase Glycolysis consists of two major phases Energy investment phase Energy payoff phase 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

A closer look at the

Phosphoglucoisomerase 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 energy investment phase

1, 3-Bisphosphoglycerate 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 payoff phase

Concept 9.3: The citric acid cycle completes the energy-yielding oxidation of organic molecules Takes place in the matrix of the mitochondrion

Before the citric acid cycle can begin Pyruvate must first be converted to acetyl CoA, which 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

Citric Acid cycle Figure 9.12 Figure 9.12 Acetyl CoA Oxaloacetate 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

Concept 9.4: During oxidative phosphorylation, chemiosmosis couples electron transport to ATP synthesis NADH and FADH2 Donate electrons to the electron transport chain, which powers ATP synthesis via oxidative phosphorylation

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: 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

At certain steps along the electron transport chain Electron transfer causes protein complexes to pump H+ from the mitochondrial matrix to the intermembrane space

The resulting H+ gradient Stores energy Drives chemiosmosis in ATP synthase 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

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

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

In the absence of oxygen Concept 9.5: 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 fermentation

Glycolysis Can produce ATP with or without oxygen, in aerobic or anaerobic conditions Couples with fermentation to produce ATP

Fermentation consists of Types of Fermentation Fermentation consists of Glycolysis plus reactions that regenerate NAD+, which can be reused by glyocolysis

(a) Alcohol fermentation (b) Lactic acid 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

Fermentation and cellular respiration 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

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

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 + –