9 Pathways that Harvest Chemical Energy Valencia College
9 Pathways that Harvest Chemical Energy Chapter objectives: How Does Glucose Oxidation Release Chemical Energy? What Are the Aerobic Pathways of Glucose Metabolism? How Does Oxidative Phosphorylation Form ATP? How Is Energy Harvested from Glucose in the Absence of Oxygen? How Are Metabolic Pathways Interrelated and Regulated?
9.1 How Does Glucose Oxidation Release Chemical Energy? Fuels are: Molecules, whose energy is stored in covalent bonds, can be released and transformed for use in organisms The most common fuel in organisms is glucose. Other molecules are first converted into glucose or other intermediate compounds.
9.1 How Does Glucose Oxidation Release Chemical Energy? Five Principles governing metabolic pathways: 1. Complex chemical transformations occur in a series of reactions called pathways 2. Each reaction is catalyzed by a specific enzyme 3. Metabolic pathways are similar in all organisms from bacteria to humans 4. In eukaryotes, metabolic pathways are compartmentalized in organelles 5. Each pathway is regulated by key enzymes, that can be activated or inhibited controlling the speed of reactions
9.1 How Does Glucose Oxidation Release Chemical Energy? The Burning or Metabolism of Glucose releases energy: C H O 6O 6CO + H O + 6 12 6 + 2 2 6 2 ( G = -686 Kcal / mol) free energy Glucose metabolism pathway traps the free energy in ATP: ADP + Pi + free energy ATP
9.1 How Does Glucose Oxidation Release Chemical Energy? ΔG is the change in free energy ΔG from complete combustion of glucose = 686 kcal/mol Highly exergonic; drives endergonic formation of many ATP molecules.
9.1 How Does Glucose Oxidation Release Chemical Energy? Three metabolic pathways are involved in capturing the energy of glucose: 1. Glycolysis converts glucose to pyruvate 2. Cellular respiration aerobic and converts pyruvate into H 2 O, CO 2, and ATP 3. Fermentation anaerobic and converts pyruvate into lactic acid or ethanol, CO 2, and ATP
Figure 9.1 Energy for Life 6CO 2 + 6H 2 O C 6 H 12 O 6 + 6O 2
9.1 How Does Glucose Oxidation Release Chemical Energy? If O 2 is present (aerobic) glycolysis is followed by three pathways of cellular respiration: Pyruvate oxidation Citric acid cycle Electron transport chain If O 2 is not present, pyruvate from glycolysis is metabolized by fermentation.
9.1 How Does Glucose Oxidation Release Chemical Energy? Oxidation / Reduction Reactions Redox reactions: One substance transfers electrons to another substance Oxidation: Loss of one or more electrons Also occurs if hydrogen atoms are gained or lost (H = H + + e - ) Reduction: Gain of one or more electrons by an atom, ion, or molecule
9.1 How Does Glucose Oxidation Release Chemical Energy? Oxidation and reduction always occur together. The reactant that becomes reduced is the oxidizing agent. The reactant that becomes oxidized is the reducing agent.
Oxidation and Reduction Are Coupled Lost electrons (Glucose) (e - donor) (e - acceptor) Gained electrons
9.1 How Does Glucose Oxidation Release Chemical Energy? In glucose combustion, glucose is the reducing agent (electron donor), O 2 is the oxidizing agent (electron acceptor). Energy is transferred in a redox reaction. Energy in the reducing agent (glucose) is transferred to the reduced product.
Figure 9.2 Oxidation, Reduction, and Energy
9.1 How Does Glucose Oxidation Release Chemical Energy? Coenzyme (Nicotinamide adenine dinucleotide) NAD + is a key electron carrier in redox reactions. Two forms: NAD + (oxidized) reducing agent NADH (reduced) oxidizing agent
NAD + Is an Energy Carrier in Redox Reactions (Oxidized) (Reduced)
9.1 How Does Glucose Oxidation Release Chemical Energy? Oxygen accepts electrons from NADH + NADH + H + 1 O NAD + H O 2 2 2 + exergonic ΔG = 52.4 kcal/mol Oxidizing agent is molecular oxygen O 2
Figure 9.4 Overview of Energy-Producing Metabolic Pathways *Two pathways depending on O 2 availability
Table 9.1 The five metabolic pathways occur in different parts of the cell.
9.2 What Are the Aerobic Pathways of Glucose Metabolism? Glycolysis takes place in the cytosol: Converts glucose into pyruvate Produces a small amount of energy in the form of ATP & NADH Generates no CO 2
9.2 What Are the Aerobic Pathways of Glucose Metabolism? Glycolysis involves ten enzyme-catalyzed reactions. Energy-investing reactions one to five require ATP. Energy-harvesting reactions six to ten yield NADH and ATP. Results in: 2 molecules of pyruvate 2 molecules of ATP 2 molecules of NADH
Figure 9.5 Glycolysis Converts Glucose into Pyruvate (Part 1)
Figure 9.5 Glycolysis Converts Glucose into Pyruvate (Part 2)
Figure 9.5 Glycolysis Converts Glucose into Pyruvate (Part 3)
Figure 9.5 Glycolysis Converts Glucose into Pyruvate (Part 4)
Figure 9.5 Glycolysis Converts Glucose into Pyruvate (Part 5)
Figure 9.5 Glycolysis Converts Glucose into Pyruvate (Part 6) Each glucose molecule in glycolysis nets 2 ATP & 2 NADH & 2 Pyruvate molecules
9.2 What Are the Aerobic Pathways of Glucose Metabolism? Phosphorylation: addition of a phosphate group to a molecule. Enzyme-catalyzed (ATP Synthase) transfer of a phosphate group from a donor to ADP to form ATP is called substrate-level phosphorylation.
9.2 What Are the Aerobic Pathways of Glucose Metabolism? If O 2 is present, glycolysis is followed by three stages of cellular respiration: 1. Pyruvate oxidation, 2. The citric acid cycle and the 3. Respiratory chain / ATP synthesis.
9.2 What Are the Aerobic Pathways of Glucose Metabolism? 1. Pyruvate Oxidation: Pyruvate enters the mitochondria by active transport Links glycolysis and the citric acid cycle; occurs in the mitochondrial matrix Pyruvate is oxidized to acetate and CO 2 is released NAD + is reduced to NADH, capturing energy Some energy is stored by combining acetate and Coenzyme A (CoA) to form acetyl CoA
Figure 9.6 Changes in Free Energy During Glycolysis and the Citric Acid Cycle
9.2 What Are the Aerobic Pathways of Glucose Metabolism? 2. Acetyl CoA is the starting point of the eight step reaction cycle called the Citric acid cycle: Inputs: acetyl CoA, water and electron carriers NAD +, FAD, and GDP Energy released is captured by ADP and electron carriers NAD +, FAD, and GDP Outputs: CO 2, reduced electron carriers, and GTP, which converts ADP to ATP
Figure 9.7 Pyruvate Oxidation and the Citric Acid Cycle (Part 1) Pyruvate is oxidized to acetate and combines with Coenzyme A (CoA) yielding Acetyl CoA catalyzed by the pyruvate dehydrogenase enzyme
9.2 What Are the Aerobic Pathways of Glucose Metabolism? The citric acid cycle is in steady state: The concentrations of the intermediates don t change. The cycle continues when starting materials are available: Acetyl CoA Reoxidized electron carriers
Figure 9.7 Pyruvate Oxidation and the Citric Acid Cycle (Part 2)
9.2 What Are the Aerobic Pathways of Glucose Metabolism? The electron carriers that are reduced during the citric acid cycle must be reoxidized to take part in the cycle again. The next step is either: Fermentation if no O 2 is present Oxidative phosphorylation O 2 is present
9.3 How Does Oxidative Phosphorylation Form ATP? Oxidative phosphorylation: ATP is synthesized by reoxidation of electron carriers in the presence of O 2. Two components of the process: Electron transport Chemiosmosis
9.3 How Does Oxidative Phosphorylation Form ATP? Electron transport: Electrons from NADH and FADH 2 pass through the respiratory chain of membrane-associated carriers Electron flow results in a proton concentration gradient out of the mitochondrial matrix onto cristae membrane of the mitochondria by active transport
9.3 How Does Oxidative Phosphorylation Form ATP? The respiratory chain is located in the inner mitochondrial membrane. Energy is released as electrons are passed between carriers. Examples: protein complexes I, II, III, IV; Cytochrome c, ubiquinone (Q)
Figure 9.8 The Oxidation of NADH and FADH 2 in the Respiratory Chain
9.3 How Does Oxidative Phosphorylation Form ATP? During electron transport protons are also actively transported. Protons accumulate in the intermembrane space and create a concentration gradient and charge difference potential energy! This proton-motive force drives protons back across the membrane.
9.3 How Does Oxidative Phosphorylation Form ATP? Chemiosmosis: Protons diffuse back into the mitochondria matrix through ATP synthase, a channel gated protein. ADP + Pi ATP Diffusion is coupled to ATP synthesis.
Figure 9.9 The Respiratory Chain and ATP Synthase Produce ATP by a Chemiosmotic Mechanism (Part 1)
Figure 9.9 The Respiratory Chain and ATP Synthase Produce ATP by a Chemiosmotic Mechanism (Part 2)
9.3 How Does Oxidative Phosphorylation Form ATP? ATP synthesis is favored over ATP hydrolysis because: ATP leaves the mitochondria once made, keeping the concentration low The proton gradient is maintained by electron transport and proton pumping Humans hydrolyze about 10 25 ATP molecules daily
9.3 How Does Oxidative Phosphorylation Form ATP? ATP synthesis can be uncoupled: If a different H + diffusion channel is inserted into the mitochondrial membrane, the energy is lost as heat. The uncoupling protein thermogenin occurs in human infants and hibernating animals H + is released as heat instead of coupled to ATP synthesis
9.4 How Is Energy Harvested from Glucose in the Absence of Oxygen? Without O 2, ATP can be produced by glycolysis and fermentation. Fermentation occurs in the cytosol, to regenerate NAD +. Pyruvate from glycolysis is reduced by NAD + to NADH
9.4 How Is Energy Harvested from Glucose in the Absence of Oxygen? Lactic acid fermentation: Occurs in microorganisms, some muscle cells Pyruvate is the electron acceptor Lactate is the product and can build up resulting in acidic ph causing muscle cramps that lessens when resting
Figure 9.11 Lactic Acid Fermentation
9.4 How Is Energy Harvested from Glucose in the Absence of Oxygen? Alcoholic fermentation: Yeasts and some plant cells Requires two enzymes to metabolize pyruvate to ethanol Acetaldehyde is reduced by NADH + H +, producing NAD + and glycolysis continues
Figure 9.12 Alcoholic Fermentation C 6 H 12 O 6 ====> 2(CH 3 CH 2 OH) + 2(CO 2 ) + Energy (which is stored in ATP) Sugar ====> (Glucose) Alcohol + Carbon dioxide gas + Energy (Ethyl alcohol)
9.4 How Is Energy Harvested from Glucose in the Absence of Oxygen? Cellular respiration yields more energy than fermentation per glucose molecule. Glycolysis plus fermentation = 2 ATP Glycolysis plus cellular respiration = 32 ATP In some cells NADH must be shuttled using ATP and net result = 30 ATP
Figure 9.13 Cellular Respiration Yields More Energy Than Fermentation
9.5 How Are Metabolic Pathways Interrelated and Regulated? An interchange of molecules occurs between metabolic pathways. Pathways are interrelated by shared substances. Pathways are regulated by enzyme inhibitors.
Figure 9.14 Relationships among the Major Metabolic Pathways of the Cell
9.5 How Are Metabolic Pathways Interrelated and Regulated? Catabolic Interconversions: Polysaccharides hydrolyzed to glucose, enters glycolysis and cellular respiration Lipids broken down to: glycerol DHAP fatty acids acetyl CoA Proteins hydrolyzed to amino acids feed into glycolysis or the citric acid cycle
9.5 How Are Metabolic Pathways Interrelated and Regulated? Anabolic Interconversions: Most catabolic reactions are reversible Gluconeogenesis: Glucose is formed from the citric acid cycle and some glycolysis intermediates
9.5 How Are Metabolic Pathways Interrelated and Regulated? Catabolism and Anabolism are integrated: Negative and positive feedback controls Concentrations of biochemical molecules remain constant (e.g., glucose concentration in blood)
Figure 9.15 Regulation by Negative and Positive Feedback Compound G provides positive feedback to the enzyme catalyzing the step from D to E Compound G inhibits the enzyme catalyzing the conversion of C to F, blocking that rxn and ultimately its own synthesis
9.5 How Are Metabolic Pathways Interrelated and Regulated? Glycolysis, the citric acid cycle, and the respiratory chain are subject to allosteric regulation of key enzymes.
Figure 9.16 Allosteric Regulation of Glycolysis and the Citric Acid Cycle (Part 1) ADP or AMP activates this enzyme ATP inhibits this enzyme
Figure 9.16 Allosteric Regulation of Glycolysis and the Citric Acid Cycle (Part 2) Inhibits this enzyme Citrate inhibits phosphofructokinase Citrate activates fatty acid synthase Activates Inhibits
9.5 How Are Metabolic Pathways Interrelated and Regulated? The main control point in glycolysis is phosphofructokinase allosterically inhibited by ATP. The main control point in the citric acid cycle is isocitrate dehydrogenase inhibited by NADH and ATP.
9.5 How Are Metabolic Pathways Interrelated and Regulated? Another control point, if ATP levels are high: Accumulation of citrate diverts acetyl CoA to fatty acid synthesis, for storage. Fatty acids may be metabolized later to produce more acetyl CoA.