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Chapter 9 Cellular Respiration & Fermentation The energy stored in the organic molecules of food ultimately comes from the sun. Energy flows into an ecosystem as sunlight and exits as heat The chemical elements esse ntial to life are recycled Photosynthesis generates oxygen and organic molecules used by the mitochondria of eukaryotes as fuel for cellular respiration. Respiration breaks this fuel down, generating ATP. The waste products of this type of respiration, carbon dioxide and water, are the raw materials for photosynthesis cells harvest the chemical energy stored in organic molecules and use it to generate ATP 9.1 Catabolic Pathways yield energy by oxidizing organic fuels catabolic processes, ones that release stored energy by breaking down complex molecules, are central to cellular respiration. Electron transfer plays a major role in these pathways. Catabolic Pathways and the Production of ATP organic compounds possess potential energy as a result of the arrangement of electrons in the bonds between their atoms. Compounds that can participate in exergonic reactions act as fuels. With the help of enzymes, a cell can break down complex organic molecules that are rich in PE to simpler waste products that have less PE. Some of the energy is converted to do work, while the rest is dissipated as heat One catabolic process, fermentation (anaerobic respiration), is a partial degradation of sugars or other organic fuel that occurs without the use of oxygen Aerobic respiration is the most prevalent and efficient catabolic pathway in which oxygen is consumed as a reactant along with the organic fuel. Cellular respiration includes both aerobic & anaerobic processes Organic Compounds + Oxygen Carbon Dioxide + Water + Energy The breakdown of organic fuel is exergonic (-G means that the products store less energy than the reactants & the reaction can occur spontaneously, without input of energy) Catabolism is linked to work by ATP. To keep working, cells must regenerate its supply of ATP from ADP & P1. Redox Reactions: Oxidation and Reduction Catabolic pathways that decompose organic fuel yields energy due to the transfer of electrons during the chemical reactions. The relocation of electrons releases energy stored in organic molecules, and this energy is used to synthesize ATP The Principle of Redox (oxidation-reduction reactions) In a redox reaction, the loss of electrons from one substance is oxidation, and the addition of electrons to another substance is reduction. The electron donor is the reducing agent. It loses an electron, becoming more positive, so it is oxidized. The electron acceptor is the oxidizing agent. It oxidizes the reducing agent by taking its electron, becoming more negative, so it is reduced Not all redox reactions involve the complete transfer of electrons from one substance to another. Some modify the degree of electron sharing in covalent bonds The atoms in methane are about equally electronegative. When CH4 reacts with O2, forming CO2, electrons end up shared less equally between CO2 & its O2 covalent partners, which are very electronegative. So the C atom has partially lost its shared eWhen O2 reacts with the H in CH4, forming H2O, the eof the covalent bonds spend more time near the O2, so O2 has partially gained e-. O2 is one of the most powerful oxidizing agents since it is so electronegative E must be added to pull an e- away from an atom, so the more electronegative an atom, the more energy is required to take an e- away from it. An e- loses PE when it shifts from a less electronegative atom towards a more electronegative one. A redox reaction that moves e- closer to oxygen releases chemical energy that can be put to work Oxidation of Organic Fuel Molecules During Cellular Respiration The organic fuel is oxidized and the O2 is reduced. The e- lose PE along the way, and E is released Organic molecules that have a lot of H are great fuels because their bonds are a source of “hilltop” e-, whose E may be released as these e- “fall” down an E gradient when they’re transferred to O2. H is transferred from the organic fuel to O2. The E state of the e- changes as H (along with its e-) is transferred to O2. Oxidation of organic fuel transfers e- to a lower E state, freeing E that becomes available for ATP synthesis The main energy-yielding foods, carbs and fats, are reservoirs of e- associated with H. Once organic fuel is taken in, enzymes in cells will lower the barrier of activation energy that holds back the flood of e- to a lower E state, allowing the fuel to be oxidized in a series of steps Stepwise Energy Harvest via NAD+ and the Electron Transport Chain Cell respiration doesn’t oxidize glucose in a single explosive step, because it can’t be harnessed efficiently for constructive work. Instead, the organic fuels are broken down in a series of steps, each one catalyzed by an enzyme At key steps, e- are stripped from the glucose. Each e- travels with a H+ (proton) The H aren’t transferred directly to O2, but instead are passed to an electron carrier, a coenzyme called NAD+, which can cycle easily between oxidized (NAD+) and reduced (NADH) states. It is an oxidizing agent during respiration. NAD+ is the most versatile e- acceptor in cell respiration and functions in several redox steps during the breakdown of glucose NAD+ traps electrons from organic molecules. Enzymes called dehydrogenases remove a pair of H atoms (2 e- & 2 p+) from the substrate, thereby oxidizing it. The enzyme delivers the 2 e- & 1 p+ to its coenzyme, NAD+. The other p+ is released as an H+ into the surrounding solution By receiving 2 e- but only 1+, NAD+ has its charge neutralized when it’s reduced to NADH e- lose very little of their PE when they’re transferred from glucose to NAD+. Each NADH molecule formed during respiration represents stored E that can be tapped to make ATP when the e- complete their “fall” down an E gradient from NADH to O2. The e- that are extracted from glucose & stored as PE in NADH reaches O2 Cell respiration brings H & O2 together to form water, but the H that reacts with O2 is derived from organic molecules. Instead of occurring in one explosive reaction, respiration uses an electron transport chain to break the fall of e- to O2 into several energy-releasing steps. An electron transport chain consists of a number of molecules, mostly proteins, built into the inner membrane of the mitochondria of eukaryotic cells. e- removed from glucose are shuttled by NADH to the “top,” higher-E end of the chain. At the “bottom,” lower-E end, O2 captures these e- along with H+, forming H2O e- transfer from NADH to O2 is an exergonic reaction with DG = -53 kcal/mol. Instead of this E being released & wasted in a single explosive step, e- cascade down the chain from one carrier molecule to the next in a series of redox reactions, losing a small amount of energy with each step until they finally reach O2, the terminal e- acceptor. Each “downhill” carrier is more electronegative (more capable of oxidizing) than its “uphill” neighbor. The e- removed from glucose by NAD+ fall down an E gradient in the electron transport chain to a far more stable location in the electronegative O2. Most e- travel down this downhill route: glucose O2 pulls e- down the chain in an E-yielding → NADH →electron transport chain→O2 tumble The Stages of Cellular Respiration: A Preview The harvesting of energy from glucose by cell respiration is a cumulative function of 3 metabolic stages 1. Glycolysis- begins degradation process in cytosol by breaking glucose into two molecules of pyruvate, which enters the mitochondria. Note: cell respiration includes only steps 2 &3. Glycolysis is not a part of cell respiration, but respiring cells derive energy from glucose using glycolysis to produce the starting material for the citric acid cycle 2. a. Pyruvate oxidation- pyruvate enters the mitochondria & is oxidized into acetacetyl CoA, which enters the citric acid cycle b. Citric acid cycle- the breakdown of glucose to CO2 is completed. Substrate-level phosphorylation- mode of ATP synthesis that occurs when an enzyme transfers a phosphate group from a substrate molecule to ADP, rather than adding an inorganic P1 to ADP as in oxidative phosphorylation; ATP is generates as an intermediate during the catabolism of glucose; produces some ATP 3. Oxidative phosphorylation- mode of ATP synthesis powered by the redox reactions of the e- transport chain a. e- transport- the e- transport chain accepts the e- from the breakdown products of the first 2 stages (NADH) and passes these e- from one molecule to another. At the end of the chain, the e- are combined with O2 & H+, forming H2O. b. chemiosmosis- energy stored in the form of a hydrogen ion gradient across a membrane is used to drive cellular work such as the synthesis of ATP In eukaryotic cells, the inner membrane of the mitochondria is the site of etransport & chemiosmosis. In prokaryotes, these happen in the plasma membrane. This stage amounts for 90% of the ATP generated by respiration. For each molecule of glucose degraded into CO2 & H2O by respiration, the cell makes up to 32 molecules of ATP, each with 7.3 kcal/mol of G. Respiration cashes in the large quantity of E stored in a single molecule of glucose for the small change of many molecules of ATP 2. 3. 4. 9.2 Glycolysis Harvests Chemical Energy by Oxidizing Glucose to Pyruvate Glycolysis is sugar splitting. Glucose, a 6-C sugar, is split into 2 3-C sugars, which are then oxidized and their remaining atoms rearrange to form 2 molecules of pyruvate Glycolysis is divided into two phases: 1. Energy investment phase- cell spends ATP. Phosphofructokinase, the pacemaker of glycolysis, transfers a phosphate group from ATP to the opposite end of the sugar. This is a key step for regulation of glucose. Kinases cause phospholrylation. ATP allosterically inhibits phosphofructokinase 2 ATP are invested, 2 ADP are produced All the C originally present in an intermediate is split apart, and it generates 2 3-C glucose is accounted for in the 2 molecules, which are isomers of each other. molecules of pyruvate; no C is 2. Energy payoff phase- ATP is produced by substrate-level released as CO2 during phosphorylation & NAD+ is reduced to NADH by eglycolysis. Occurs regardless of released from the oxidation of glucose. This yields 2 ATP whether O2 is present or not + 2 NADH 4 ATP and 2 NADH are produced for each pyruvate 9.3 After Pyruvate is Oxidized, the Citric Acid Cycle Completes the E-Yielding Oxidation of Organic Molecules If O2 is present, the pyruvate enters a mitochondria (in eukaryotic cells and cytosol of prokaryotic) where the oxidation of glucose is completed Oxidation of Pyruvate to Acetyl CoA (link reaction) Upon entering the mitochondria via active transport, pyruvate is first converted to acetyl CoA. This step links glycolysis & the citric acid cycle, and it is carried out by a multi-enzyme complex that catalyzes 3 reactions: 1. Pyruvate’s carboxyl group, which is already fully oxidized & thus has little chemical E, is removed & given off as a molecule of CO2. 2. The remaining 20C fragment is oxidized, forming acetate. The extracted e- are transferred to NAD+, storing E in the form of NADH (Hint: anytime CO2 leaves, the molecule has to rearrange, so NAD+ needs to come in and reduce to NADH) 3. Coenzyme A (CoA), a sulfur-containing compound from a B-vitamin, is attached via its sulfur atom to the acetate, forming acetyl CoA, which has a high PE. The reaction of acetyl CoA to yield lower-E products is very exergonic. Quick review of structure of mitochondria: The folds, cristae, help increase surface area, thus increasing respiration. The inner-membrane space is between the matrix and the outer membrane The Citric Acid Cycle 1. 2. 3. 4. 5. 6. Oxidizes organic fuel derived from pyruvate A transport protein actively transports pyruvate into the mitochondrial matrix, where the Kreb’s cycle occurs end products of the cycle are the starting products Acetyl CoA (from the oxidation of pyruvate) adds its 2-C acetyl group to oxaloacetate (4-C), producing a 6-C citrate. The CoA leaves In order to get to a 4-C molecule end product, 2 CO2s are lost, and 2 NAD+ are reduced to NADH. CoA is transferred by a phosphate group, which is added to GDP to form GTP, which can generate ATP. 2 H are transferred from an intermediate to FAD, forming FADH2 The addition of H2O rearranges the bonds in the substrate The substrate is oxidized, reducing NAD+ to NADH & regenerating oxaloacetate The cycle generates 1 ATP per turn by substrate-level phosphorylation, but most of the chemical E is transferred to NAD+ & a related e- carrier, coenzyme FAD during redox reactions. The reduced coenzymes, NADH & FADH2, shuttle their cargo of high-E e- into the e- transport chain 9.4 During Oxidative Phosphorylation, Chemiosmosis Couples Electron Transport to ATP Synthesis The Pathway of Electron Transport The e- transport chain is a collection of molecules embedded in the inner membrane the folding of the inner membrane to form cristae increases its surface area, providing space for more copies of the chain in each mitochondria. Most components of the chain are protein complexes number I – IV. Tightly bound to these proteins are prosthetic groups, nonprotein compounds essential for the catalytic function of certain enzymes During e- transport along the chain, e- carriers alternate between reduced & oxidized states as they accept & donate e-. Each component of the chain becomes reduced when it accepts e- from its uphill neighbor, which is less electronegative It then returns to its oxidized form as it passes e- to its downhill, more electronegative neighbor e- are carried by NADH and are transferred to flavoprotein, the first molecule in the e- transport chain. the e- continue along the chain, passing through a Fe-S protein then through a small hydrophobic ecarrier, ubiquinone, Most of the remaining e- carriers between Q & O2 are proteins called cytochromes, which have prosthetic groups (heme group) that accept and donate e-. The last cytochrome of the chain, cyt a3, passes its e- to O2, which is the most electronegative FADH2 is another source of e- for the transport chain. It adds e- to complex II, at a lower E level than NADH does. Although NADH & FADH2 each donate 2 electrons for O2 reduction, the e- transport chain provides less energy for ATP synthesis when the e- donor is FADH2. The e- transport chain eases the fall of e- from food to O2, breaking a large DG into a series of smaller steps that release E in manageable amounts. Chemiosmosis: the Energy-Coupling Mechanism ATP synthase is an enzyme that makes ATP from ADP & inorganic phosphate; many copies populate the inner membrane of the mitochondria ATP synthase works like an ion pump running in reverse. Ion pumps use ATP as an energy source to transport ions against their gradients. ATP synthase uses the E of an existing ion gradient to power ATP synthesis. The power source for the ATP synthase is a difference in the concentration of H+ on opposite sides of the inner mitochondrial membrane. chemiosmosis- E stored in the form of a H+ gradient across a membrane that’s used to drive cellular work (such as the synthesis of ATP) ATP synthase is a multisubunit complex with 4 main parts. Protons move one by one into binding sites on one of the parts, causing it to spin so that it catalyzes ATP production from ADP & inorganic phosphate. The inner mitochondrial membrane generates & maintains the H+ gradient that drives ATP synthesis A main function of the e- transport chain is establishing the H+ gradient. The chain is an E converter that uses the exergonic flow of e- from NADH & FADH2 to pump H+ across the membrane, from the matrix to the intermembrane space. The H+ has a tendency to move back across the membrane, diffusing with its gradient. And the ATP sythases are the only sites that provide a route through the membrane for H+. The E stored in a H+ gradient across a membrane couples the redox reactions of the e- transport chain to ATP synthesis. E- transport chain pumps H+ ions because certain members of the e- transport chain accept & release H+ along with e-. At certain steps along the chain, e- transfers cause H+ to be taken up & released into the surrounding solution. H+ is accepted from the matrix & deposited into the intermembrane space. The H+ gradient that results is the proton motive force. This force drives H+ back across the membrane through the H+ channels provided by ATP synthases Chemiosmosis is an E-coupling mechanism that uses E stored in the form of an H+ gradient across a membrane to drive cell work An Accounting of ATP Production by Cellular Respiration the overall function of cell respiration is harvesting the E of glucose for ATP synthesis During respiration, the E flows in this sequence: glucose NADH e- transport chain proton-motive force ATP 4 ATP are produced directly by substrate-level phosphorylation during glycolysis & the Kreb’s cycle Each NADH that transfers a pair of e- from glucose to the e- transport chain contributes enough to the proton-motive force to generate a max of 3 ATP Each FADH2 can be used to generate a max of 2 ATP There are three reasons that we cannot state an exact number of ATP molecules generated by one molecule of glucose. 1. Phosphorylation and the redox reactions are not directly coupled to each other, so the ratio of number of NADH to number of ATP is not a whole number. 2. The ATP yield varies slightly depending on the type of shuttle used to transport electrons from the cytosol into the mitochondrion • The mitochondrial inner membrane is impermeable to NADH, so the two electrons of the NADH produced in glycolysis must be conveyed into the mitochondrion by one of several electron shuttle systems 3. The proton-motive force generated by the redox reactions of respiration may drive other kinds of work, such as mitochondrial uptake of pyruvate from the cytosol Complete oxidation of glucose releases 686 kcal/mol. About 34% of the potential chemical energy in glucose has been transferred to ATP Cell respiration is very efficient at its energy conversion the rest of the E stored in glucose is lost as heat 9.5 Fermentation & Anaerobic Respiration Enable Cells to Produce ATP without the Use of Oxygen without the electronegative O2 to pull e- down the transport chain, oxidative phosphorylation ceases. in anaerobic respiration, which takes place in prokaryotes that live without oxygen, the organisms have an e- transport chain but don’t use O2 as the final e- acceptor. Less electronegative substances can also serve as final e- acceptors. Fermentation harvests chemical E without cell respiration – without the use of O2 or e- transport chains. Fermentation is an extension of glycolysis that allows continuous generation of ATP by the substrate-level phosphorylation of glycolysis. This requires a sufficient supply of NAD+ to accept e- during the oxidation step of glycolysis. Without being able to recycle NAD+ from NADH, glycolysis would deplete the cell’s supply of NAD+ by reducing it all to NADH & would shut itself down for lack of an oxidizing agent. e- are transferred from NADH to pyruvate. Types of Fermentation Fermentation consists of glycolysis plus reactions that regenerate NAD+ by transferring e- from NADH to pyruvate The NAD+ can then be reused to oxidize sugar by glycolysis Two common types are alcohol fermentation & lactic acid fermentation, which differ in the end products formed from pyruvate in alcohol fermentation, pyruvate is converted to ethanol (ethyl alcohol) in 2 steps. 1. CO2 is released from the pyruvate, which is converted to the e-C compound acetaldehyde 2. acetaldehyde is reduced by NADH to ethanol. This regenerates the supply of NAD+ needed for the continuation of glycolysis many bacteria carry out alcohol fermentation under anaerobic conditions. Yeast, a fungus, carries it out. The CO2 bubbles generated by baker’s yeast allow the bread to rice. in lactic acid fermentation, pyruvate is reduced directly by NADH to form lactate (lactic acid ion) as an end product, with no release of CO2. lactic acid fermentation by certain fungi & bacteria is used to make cheese & yogurt human muscles make ATP by lactic acid fermentation when O2 is scarce. This occurs during strenuous exercise, when sugar catabolism for ATP production outpaces the muscle’s supply of O2 from the blood. The cells switch to fermentation. The excess lactate is carried away by the blood to the liver, where it’s converted back to pyruvate by liver cells. Because O2 is available, this pyruvate can then enter the mitochondria in liver cells & complete cell respiration Comparing Fermentation with Anaerobic & Aerobic Respiration Aerobic the final e- acceptor is O2 • yields up to 16 times as much ATP per glucose molecules than fermentation does • up to 32 molecules of ATP produced • e- carried by NADH are transferred to an etransport chain, where they move stepwise down a series of redox reactions to the final e- acceptor • passage of e- from NADH to the e- transport chain regenerates the NAD+ required for glycolysis & pays an ATP bonus when the step-wise e- transport from this NADH to O2 drives oxidative phosphorylation • cell pathways for producing ATP by harvesting chemical energy of food • use glycolysis to oxidize organic fuels to pyruvate, with net production of 2 ATP by substrate-level phosphorylation •NAD+ is the oxidizing agent that accepts e- from food during glycolysis Fermentation • The final e- acceptor is an organic molecule such as pyruvate (lactic acid fermentation) or acetaldehyde (alcohol fermentation) Obligate anaerobes carry out only fermentation of anaerobic respiration. They can’t survive in the presence of O2, which can be toxic if protective systems aren’t present in the cell. Facultative anaerobes can make enough ATP to survive using either fermentation or respiration. Pyruvate is a fork in the metabolic road that leads to two alternative catabolic routes. Under aerobic conditions, pyruvate can be converted to acetyl CoA, and oxidation continues in the citric cycle via aerobic respiration. Under anaerobic conditions, lactic acid fermentation occurs: pyruvate is diverted from the citric acid cycle, serving instead as an e- acceptor to recycle NAD+. To make the same amount of ATP, it has to consume sugar at a much faster rate when fermenting than respiring o ex: yeasts, many bacteria, cells of the vertebrae brain, muscle cells. Anaerobic • the final e- acceptor is another molecule that is less electronegative than O2 The Evolutionary Significance of Glycolysis Ancient prokaryotes are thought to have used glycolysis to make ATP long before O2 was present in Earth’s atmosphere. They generated ATP only from glycolysis. The fact that glycolysis is the most widespread metabolic pathway suggests that it evolved very early in the history of life. The cytosolic location of glycolysis implies that it doesn’t require any membrane bound organelles of the eukaryotic cell 9.6 Glycolysis and the Citric Acid Cycle Connect to Many Other Metabolic Pathways The Versatility of Catabolism Free glucose molecules aren’t common in the diets of heterotrophs, who obtain most of their calories from other organic molecules such as fats, proteins, disaccharides, and starch by cell respiration to make ATP. Glycolysis can accept many carbohydrates. o Starch (storage polysaccharide for plants) is hydrolyzed to glucose o Glycogen (storage polysaccharide in animals’ livers) is hydrolyzed to glucose between meals as fuel for respiration Proteins must be digested to their basic amino acids before they can be used for fuel. Many of the amino acids are used by the organism to build new proteins. Amino acids present in excess are converted by enzymes to intermediates of glycolysis & the citric acid cycle. o Before amino acids can feed into glycolysis or the citric acid cycle, their amino groups must undergo deanimation (remove it). The nitrogenous refuse is excreted from the animal as waste. Catabolism can also harvest E stored in fats from food or storage cells in the body. Fats make great fuel, mainly due to their chemical structure & high E level of their e-. A gram of fat oxidized by respiration produces more than twice as much ATP as a gram of carbs. After fats are digested to glycerol & fatty acids, the glycerol is converted to G3P. Most of the E of a fat is stored in the fatty acids. o Beta oxidation is a metabolic sequence that breaks the fatty acids down to 2-C fragments, which enter the citric acid cycle as acetyl CoA. NADH & FADH2 are also generated; they can enter the e- transport chain, leading to further ATP production Biosynthesis (Anabolic Pathways) Cells need substance as well as energy. Not all organic molecules of food are destined to be oxidized as fuel to make ATP. Food must provide the C-skeletons that cells require to make their own molecules. Some organic monomers from digestion can be used directly, like amino acids from the hydrolysis of proteins. The body needs specific molecules that aren’t present in food. Compounds formed as intermediates of glycolysis & the citric acid cycle can be diverted into anabolic pathways as precursors from which the cell can synthesize the molecules it requires. Anabolic or biosynthetic pathways consume ATP. o Ex: humans can make 10 types of amino acids in proteins by modifying compounds tapped away from the citric acid cycle. o Ex: Glucose can be made from pyruvate, and fatty acids can be synthesize from acetyl CoA Glycolysis & the citric acid cycle function as metabolic interchanges that enable cells to convert some kinds of molecules to others. Regulation of Cellular Respiration via Feedback Mechanisms Cells don’t waste energy making excess substances o Ex: If there’s an excess of a certain amino acid, the anabolic pathway that synthesizes that amino acid from an intermediate of the citric acid cycle is switched off Feedback inhibition regulates cell respiration. The end product of the anabolic pathway inhibits the enzyme that catalyzes an early step of the pathway. This prevents the needless diversion of key metabolic intermediates from uses that are more important Cells control their catabolism. If they’re working hard & its ATP concentration begins to drop, respiration speeds up. When there’s plenty of ATP, respiration slows down, sparing valuable organic molecules for other functions. Phosphofructokinase is considered as the pacemaker of respiration. It responds to inhibitors & activators that help set the pace of glycolysis & the citric acid cycle. It is an allosteric enzyme with receptor sites for specific inhibitors & activators. It is inhibited by ATP & stimulate by AMP, which comes from ADP. o As ATP accumulates, inhibition of the enzyme slows down glycolysis. o The enzyme becomes active again as cell work converts ATP to ADP to AMP faster than ATP is being regenerated It’s sensitive to citrate, the 1st product of the citric acid cycle. If citrate accumulates in mitochondria, some of it passes into the cytosol & inhibits it. This helps coordinate the rates of glycolysis & the citric acid cycle. As citrate accumulates, glycolysis slows down, & the supply of acetyl groups to the citric acid cycle decreases. If citrate consumption increases, glycolysis accelerates & meets the demand. The E that keeps organisms alive is released, not produced by cell respiration. We are tapping E that was stored in food by photosynthesis. o