Cellular Respiration and Fermentation 9 Cellular Respiration and Fermentation Lecture Presentation by Cindy S. Malone, PhD, California State University Northridge

Please make sure to highlight all the terms in blue.

An Overview of Cellular Respiration All organisms use glucose to build fats, carbohydrates, and other compounds. Cells recover glucose by breaking down these molecules. Glucose is used to make ATP through cellular respiration or fermentation. Cellular respiration produces ATP from a molecule with high potential energy, usually glucose.

An Overview of Cellular Respiration Each of the four steps of cellular respiration consists of: A series of chemical reactions A distinctive starting molecule Characteristic set of products

Starch, glycogen, fats (synthesized from glucose) Figure 9.1 Energy conversion Photosynthesis Energy storage Starch, glycogen, fats (synthesized from glucose) Energy use Figure 9.1 Glucose Is the Hub of Energy Processing in Cells. Cellular Respiration Fermentation 5

What Happens When Glucose Is Oxidized? Oxygen atoms in oxygen are reduced to form water: C6H12O6  6 O2  6 CO2  6 H2O  energy glucose oxygen carbon water dioxide Glucose is oxidized through a long series of carefully controlled redox reactions. The resulting change in free energy is used to synthesize ATP from ADP and Pi. These reactions comprise cellular respiration.

The Steps of Cellular Respiration Cellular respiration is: Any set of reactions that produces ATP In an electron transport chain Cellular respiration has four steps: 1. Glycolysis Glucose is broken down to pyruvate 2. Pyruvate processing Pyruvate is oxidized to form acetyl CoA

The Steps of Cellular Respiration 3. Citric acid cycle Acetyl CoA is oxidized to CO2 4. Electron transport and chemiosmosis Compounds reduced in steps 1–3 are oxidized in reactions leading to ATP production

Cellular Respiration Interacts with Metabolic Pathways Energy and carbon: Are two fundamental requirements of cells. Need high-energy electrons for generating chemical energy in the form of ATP. Are a source of carbon-containing molecules for synthesizing macromolecules. Metabolism includes: Thousands of different chemical reactions that are either catabolic pathways or anabolic pathways.

Cellular Respiration Interacts with Metabolic Pathways Catabolic pathways Involve the breakdown of molecules and production of ATP. Often harvest stored chemical energy to produce ATP. Anabolic pathways Result in the synthesis of larger molecules from smaller components. Often use energy in the form of ATP.

Catabolic Pathways Break Down a Variety of Molecules For ATP production, cells: First use carbohydrates, then fats and finally proteins. Proteins, carbohydrates, and fats can all furnish substrates for cellular respiration.

Anabolic Pathways Synthesize Key Molecules Molecules found in carbohydrate metabolism are used to synthesize macromolecules such as: RNA DNA Glycogen or starch Amino acids Fatty acids And other cell components

Glycolysis: Processing Glucose to Pyruvate Glycolysis is: A series of 10 chemical reactions The first step in glucose oxidation All of the enzymes needed for glycolysis are found in the cytosol. In glycolysis: Glucose is broken down into two molecules of pyruvate. The potential energy released is used to phosphorylate ADP to ATP.

The Glycolysis Reactions Glycolysis consists of: An energy investment phase An energy payoff phase

The Glycolysis Reactions In the energy investment phase: 2 molecules of ATP are consumed In the energy payoff phase: Sugar is split to form two pyruvate molecules 2 molecules of NAD+ are reduced to NADH 4 molecules of ATP are formed by substrate-level phosphorylation (net gain of 2 ATP)

Feedback Inhibition Feedback inhibition occurs: When an enzyme in a pathway is inhibited by the product of that pathway. Cells that are able to stop glycolytic reactions when ATP is abundant. Can conserve their stores of glucose for times when ATP is scarce.

Feedback Inhibition Regulates Glycolysis During glycolysis, high levels of ATP inhibit: The enzyme phosphofructokinase This enzyme catalyzes one of the early reactions Phosphofructokinase has two binding sites for ATP: 1. The active site Where ATP phosphorylates fructose-6-phosphate Resulting in the synthesis of fructose-1,6-bisphosphate 2. A regulatory site

Feedback Inhibition Regulates Glycolysis High ATP concentrations cause: ATP to bind at the regulatory site Changing the enzyme’s shape Dramatically decreasing the reaction rate at the active site In phosphofructokinase: ATP acts as an allosteric regulator

ATP at regulatory site ATP at active site Figure 9.7 When ATP binds here, the reaction rate slows dramatically ATP at regulatory site Figure 9.7 Phosphofructokinase Has Two Binding Sites for ATP. Fructose-6- phosphate at active site ATP at active site 19

The Remaining Reactions Occur in the Mitochondria Pyruvate produced during glycolysis is: Transported from the cytosol Into the mitochondria Mitochondria have both inner and outer membranes. Cristae: Are layers of sac-like structures that fill the interior of the mitochondria. The mitochondrial matrix: Is inside the inner membrane But outside the cristae

Inner membrane Intermembrane space Outer membrane Figure 9.8 Cristae are sacs of inner membrane joined to the rest of the inner membrane by short tubes Matrix Cristae Inner membrane Intermembrane space Figure 9.8 The Structure of the Mitochondrion. Outer membrane 100 nm 21

Pyruvate Processing Pyruvate processing is: In the presence of O2: The second step in glucose oxidation Catalyzed by the enzyme pyruvate dehydrogenase in the mitochondrial matrix. In the presence of O2: Pyruvate undergoes a series of reactions, results in the product molecule acetyl coenzyme A (acetyl CoA)

Pyruvate Acetyl CoA Figure 9.9 Figure 9.9 Pyruvate Is Oxidized to Acetyl CoA. Pyruvate Acetyl CoA 23

The Citric Acid Cycle The third step of glucose oxidation: The acetyl CoA produced by pyruvate processing enters the citric acid cycle. Located in the mitochondrial matrix Each acetyl CoA is oxidized to two molecules of CO2 Some of the potential energy released is used to: 1. Reduce NAD+ to NADH 2. Reduce flavin adenine dinucleotide (FAD) to FADH2 Another electron carrier 3. Phosphorylate GDP to form GTP Later converted to ATP

runs twice for each glucose molecule oxidized Figure 9.10 The two red carbons enter the cycle via acetyl CoA All 8 reactions of the citric acid cycle occur in the mitochondrial matrix, outside the cristae Acetyl CoA Citrate Isocitrate In each turn of the cycle, the two blue carbons are converted to CO2 -Ketoglutarate Oxaloacetate The CITRIC ACID CYCLE runs twice for each glucose molecule oxidized Figure 9.10 The Citric Acid Cycle Completes the Oxidation of Glucose. In the next cycle, this red carbon becomes a blue carbon Succinyl CoA Malate Each reaction is catalyzed by a different enzyme Succinate Fumarate 25

The Citric Acid Cycle Regulation and Summary The citric acid cycle can be turned off at multiple points via several different mechanisms of feedback inhibition. Citric acid cycle starts with acetyl CoA and ends with CO2. The potential energy that is released is used to produce NADH, FADH2, and ATP. When energy supplies are high the cycle slows down.

This step is regulated by ATP Figure 9.11 These steps are also regulated via feedback inhibition, by NADH and ATP This step is regulated by ATP Figure 9.11 The Citric Acid Cycle Is Regulated by Feedback Inhibition. 27

Glucose Oxidation Summary Glucose oxidation produces: ATP, NADH, FADH2, and CO2 Glucose is completely oxidized to: Carbon dioxide via glycolysis The subsequent oxidation of pyruvate Then the citric acid cycle In eukaryotes, glycolysis occurs in the cytosol. Pyruvate oxidation and the citric acid cycle take place in the mitochondrial matrix.

Figure 9.12 Figure 9.12 Glucose Oxidation Produces ATP, NADH, FADH2, and CO2. Cytosol Mitochondrial matrix 29

Free Energy Changes, NADH, and FADH2 Each glucose molecule that is oxidized to 6 CO2: Reduces 10 molecules of NAD+ to NADH 2 molecules of FAD to FADH2 Produces 4 molecules of ATP By substrate-level phosphorylation The ATP can be used directly for cellular work. Most of glucose’s original energy is contained in: The electrons transferred to NADH and FADH2 Which then carry them to oxygen, the final electron acceptor.

Free-energy change relative to glucose (kcal/mol) Figure 9.13 GLYCOLYSIS PYRUVATE PROCESSING CITRIC ACID CYCLE Free-energy change relative to glucose (kcal/mol) In each of these drops, energy is transferred to energy-storing molecules ATP, NADH, GTP, or FADH2 Figure 9.13 Free Energy Changes as Glucose Is Oxidized. Oxidation of glucose  31

The Electron Transport Chain During the fourth step in cellular respiration: The high potential energy of the electrons carried by NADH and FADH2 is gradually decreased as they move through a series of redox reactions. The proteins involved in these reactions make up: An electron transport chain (ETC) O2 is the final electron acceptor The transfer of electrons along with protons to oxygen forms water.

Free-energy change relative to O2 (kcal/mol) Figure 9.14 Complex I Complex II ETC reactions take place in the inner membrane and cristae of the mitochondrion Complex III Free-energy change relative to O2 (kcal/mol) Complex IV Figure 9.14 A Series of Reduction–Oxidation Reactions Occur in an Electron Transport Chain. FMN: flavin-containing prosthetic group in flavoprotein FeS: protein with an iron–sulfur cofactor Cyt: protein with a heme prosthetic group Q: ubiquinone, a nonprotein coenzyme Reduction-oxidation reactions  33

ATP Yield from Cellular Respiration The vast majority of the “payoff” from glucose oxidation occurs via oxidative phosphorylation. ATP synthase produces: 25 of the 29 ATP molecules Produced per glucose molecule during cell respiration

Figure 9.19 Electron transport chain Oxidative phosphorylation Electrons Figure 9.19 ATP Yield during Cellular Respiration. Maximum yield of ATP per molecule of glucose: 29 Cytosol Mitochondrial matrix 35

Aerobic and Anaerobic Respiration All eukaryotes and many prokaryotes use: Oxygen as the final electron acceptor Of electron transport chains in aerobic respiration Some prokaryotes: Especially those in oxygen-poor environments Use other electron acceptors in anaerobic respiration

Fermentation Cellular respiration cannot occur without oxygen. Metabolic pathway that regenerates NAD+ from NADH Glycolysis can produce ATP in the absence of oxygen Fermentation occurs: When pyruvate or a molecule derived from pyruvate Accepts electrons from NADH This transfer of electrons oxidizes NADH to NAD+: Glycolysis can continue to produce ATP Via substrate-level phosphorylation

Different Fermentation Pathways In lactic acid fermentation: Pyruvate produced by glycolysis Accepts electrons from NADH Lactate and NAD+ are produced Lactic acid fermentation occurs in muscle cells In alcohol fermentation: Pyruvate is enzymatically converted to acetaldehyde and CO2 Acetaldehyde accepts electrons from NADH Ethanol and NAD+ are produced Alcohol fermentation occurs in yeast

Please make sure to read the corresponding textbook chapter.