Chapter 9: Cellular Respiration To perform their many tasks, living cells require energy from outside sources. Energy stored in food utimately comes from the sun. Photosynthesis makes the raw materials needed for respiration. 9.1 The Principles of Energy Harvest catabolic pathways: cellular respiration => complete breakdown of organic molecules using O2 fermentation => partial breakdown of sugars with no O2. Both yield energy, but cellular respiration is more efficient. In eukaryotic cells, mitochondria are the site of most of the processes of cellular respiration. The overall process is: organic compounds + O2 CO2 + H2O + energy (ATP + heat). Carbohydrates, fats, and proteins can all be used as the fuel, but it is most useful to consider glucose. C6H12O6 + 6O2 6CO2 + 6H2O + Energy (ATP + heat) The catabolism of glucose is exergonic with a G of 686 kcal per mole of glucose. Review redox reactions. Cellular respiration does not oxidize glucose in a single step that transfers all the hydrogen in the fuel to oxygen at one time. Rather, glucose and other fuels are broken down in a series of steps, each catalyzed by a specific enzyme. 2 electrons are stripped from glucose by dehydrogenase. They are transferred with one H + to a coenzyme called NAD + (nicotinamide adenine dinucleotide) => glucose is oxidized, NAD+ reduced to NADH. The other H + is released to the surrounding solution. The stored energy in NADH is used to make ATP as electrons move along electron transport chain. Oxygen awaits at the bottom to accept electrons and H+ (forms water). Cellular Respiration-1
Downhill route of electron: food NADH electron transport chain oxygen. Stages of cellular respiration: a preview. 1) Glycolysis => occurs in the cytoplasm => anaerobic portion => breaks down glucose into two molecules of pyruvate 2) A. Pyruvate oxidation into acetyl CoA B. Citric acid cycle => occurs in the mitochondrial matrix => aerobic => completes the breakdown of glucose by oxidizing a derivative of pyruvate to carbon dioxide 3) Oxidative phosphorylation => ETC and chemiosmosis to form ATP => occurs on inner membrane (cristae) of mitochondria => produces almost 90% of the ATP generated by respiration Some ATP is also formed directly during glycolysis and the citric acid cycle by substrate-level phosphorylation => enzyme transfers a phosphate group from an organic substrate to ADP, forming ATP For each molecule of glucose degraded to carbon dioxide and water by respiration, the cell makes up to 38 ATP, each with 7.3 kcal/mol of free energy. (According to 10thED textbook max 32 => there is a cost of transporting substances, such as pumping pyruvate into the mitochondrion, to where they need to be) Cellular Respiration-2
9.2 Glycolysis During glycolysis, glucose (6-C) is split into two three-carbon sugars (energy investment phase-2atp are used). These smaller sugars are oxidized and rearranged to form two molecules of pyruvate, the ionized form of pyruvic acid (energy payoff phase-4atp and 2NADH produced). Each of the ten steps in glycolysis is catalyzed by a specific enzyme. The net yield from glycolysis is 2 ATP and 2 NADH per glucose. No CO2 is produced during glycolysis. Glycolysis is anaerobic. Cellular Respiration-3
9.3 The Citric Acid Cycle Also called the Krebs cycle in honor of Hans Krebs (1930s). If oxygen is present, pyruvate enters the mitochondrion where enzymes of the citric acid cycle complete the process. After pyruvate enters the mitochondria via active transport, it is converted to acetyl coenzyme A (acetyl CoA). Done in 3 rxns by an enzyme complex: 1. A carboxyl group is removed as CO2 (waste). 2. The remaining two-carbon fragment is oxidized to form acetate. An enzyme transfers the pair of electrons to NAD+ to form NADH. 3. Acetate combines with coenzyme A to form acetyl CoA. Citric Acid Cycle: The acetyl group (2C) of acetyl CoA joins the cycle by combining with the compound oxaloacetate (4C), forming citrate (6C). The next seven steps decompose the citrate back to oxaloacetate. The cycle generates 2 CO2, one ATP, 3NADH, 1FADH2, per turn (for each pyruvate). NADH and FADH2 proceed to the electron transport chain and CO2 is released as a waste product. Cellular Respiration-4
9.4 Oxidative Phosphorylation The electron transport chain is a collection of molecules embedded in the cristae. Most components of the chain are proteins bound to prosthetic groups, nonprotein components essential for their function (multiprotein complexes I-IV). Electrons drop in free energy as they pass down the electron transport chain. Oxygen is final electron acceptor which also picks up 2H + to form water. FADH2 adds electrons at Complex II (which results in less energy) The exergonic flow of the electrons along the ETC is used to pump H+ from the matrix to the intermembrane space. This establishes a gradient (protonmotive force). The protons pass back to the matrix through a channel in ATP synthase => chemiosmosis Structure of ATP synthase: Protons flow down between the stator and rotor, causing the rotor and rod to rotate. The spinning rod causes conformational changes in the stationary knob, activating three catalytic sites in the knob where ADP and inorganic phosphate combine to make ATP. Prokaryotes also generate H + gradients across their plasma membrane. They use proton-motive force to generate ATP, pump substances across membranes, and rotate their flagella. Cellular Respiration-5
Here is an accounting of ATP production by cellular respiration. Four ATP molecules during glycolysis and the citric acid cycle. Each NADH contributes enough energy to the proton-motive force to generate a maximum of 3 ATP. Each FADH2 about 2 ATP. Total ATP for glucose: about 36-38 (but again, there is a cost of transport/shuttling, etc so more like 30-32) Efficiency: 34%; rest lost as heat (some used to maintain body temp) 9.5 Fermentation Cellular respiration can be aerobic or anaerobic. Anaerobic respiration also involves use of an ETC but oxygen is not the final electron acceptor (ex. sulfate). Another anaerobic process is fermentation. Fermentation => partial breakdown of organic substances without oxygen or an ETC Common types: alcohol fermentation => pyruvate is converted to ethanol CO2 removed from pyruvate and is converted to acetaldehyde acetaldehyde is reduced by NADH to ethanol. ex. brewing and winemaking by yeast Cellular Respiration-6
lactic acid fermentation => pyruvate is reduced directly by NADH to form lactate (the ionized form of lactic acid); no CO2. ex. cheese and yogurt; human muscle cells when O2 is scarce Bottom line: NAD+ is regenerated so glycolysis can continue. Fermentation does that in the absence of oxygen. Obligate anaerobes => cannot survive in the presence of oxygen facultative anaerobes => can survive using either fermentation or respiration (depending on presence of oxygen) ex. yeast and many bacteria human muscle cells can behave as facultative anaerobes Evolutionary significance of glycolysis: First prokaryotes may have generated ATP exclusively from glycolysis (oxygen was not present in early atmosphere). Most widespread pathway and occurs in the cytosol without membrane-enclosed organelles suggests that glycolysis evolved early in the history of life. Cellular Respiration-7
9.6 Connection to Other Metabolic Pathways Glycolysis can accept a wide range of carbohydrates for catabolism. Carbs can be hydrolyzed or modified to glucose monomers that enter glycolysis. Proteins must first be digested to individual amino acids and amino groups removed (as ammonia, urea). The carbon skeletons are modified and enter the cycle. Fats must be digested to glycerol (converted to G3P) and fatty acids (split into two-carbon fragments-beta oxidation- to enter as acetyl CoA). NADH and FADH2 are also generated to enter ETC. Biosynthesis: Food also provides the substances necessary for cells building blocks. Ex. Amino acids to build proteins. Feedback mechanisms control cellular respiration. When ATP levels drop, respiration rate increases. When ATP levels high, respiration rate decreases. One important enzyme allosterically regulated is phosphofructokinase (step 3 glycolysis). When ATP or citrate levels are high => inhibition slows glycolysis; AMP levels high => glycolysis speeds up. Cellular Respiration-8