Chapter 23 Metabolism and Energy Production PDF

Chapter Twenty Three Metabolism and Energy Production HW (no credit): 1-16, 25-32, 35-39, 45-48, 53-65, 67, 73, 75, 77, 79, 81, 83, 87, 91  The Citric Acid Cycle The citric acid cycle is a series of reactions that connects the intermediate acetyl CoA from stage 2 wit...

Chapter Twenty Three Metabolism and Energy Production HW (no credit): 1-16, 25-32, 35-39, 45-48, 53-65, 67, 73, 75, 77, 79, 81, 83, 87, 91  The Citric Acid Cycle The citric acid cycle is a series of reactions that connects the intermediate acetyl CoA from stage 2 with electron transport and the synthesis of ATP in stage 3. Stages of Catabolism  The Citric Acid Cycle (Stage 3) ►operates under aerobic conditions. ►oxidizes the two-carbon acetyl group in acetyl CoA to CO2. ►is named from citric acid, formed in the first reaction. ►is also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle.  Citric Acid Cycle Overview ► In the citric acid cycle, eight reactions oxidize acetyl CoA, producing CO2 and the high- energy compounds FADH2, NADH, and GTP. ► Reactions involved in the citric acid cycle include condensation, dehydration, hydration, oxidation, reduction, and hydrolysis.  Reaction 1: Formation of Citrate In the first reaction (condensation)of the citric acid cycle, ►citrate synthase catalyzes the condensation of an acetyl group (2C) from acetyl CoA with oxaloacetate (4C) to yield citrate (6C) and coenzyme A. ►the energy to form citrate is provided by the hydrolysis of the high-energy thioester bond in acetyl CoA.  Reaction 2: Isomerization In reaction 2 (isomerization) of the citric acid cycle, ► citrate rearranges to isocitrate, a secondary alcohol. ► aconitase catalyzes the isomeration of citrate (tertiary alcohol) to isocitrate (secondary alcohol). Reaction 3: Oxidation, Decarboxylation In reaction 3, isocitrate undergoes oxidation and decarboxylation by isocitrate dehydrogenase. ►One carbon is removed by converting a carboxylate group (COO−) to CO2. ►The dehydrogenase removes hydrogen ions and electrons, used to reduce NAD+ to NADH and H+.  Reaction 4: Oxidation, Decarboxylation In reaction 4, oxidation and decarboxylation catalyzed by α- ketoglutarate dehydrogenase, ► α-ketoglutarate (5C) undergoes decarboxylation to yield (4C) succinyl CoA. ► oxidation of the thiol group (— SH) in HS — CoA provides hydrogen that is transferred to NAD+ to form a second molecule of NADH and H+.  Reaction 5: Hydrolysis In reaction 5, hydrolysis catalyzed by succinyl CoA synthetase, ► hydrolysis of the thioester bond in succinyl CoA yields succinate and HS — CoA. ► energy from hydrolysis is transferred to the condensation of phosphate and GDP forming GTP, a high-energy compound similar to ATP.  Reaction 6: Oxidation In reaction 6, oxidation catalyzed by succinate dehydrogenase, ► succinate is oxidized to fumarate, a compound with a C = C bond. ► 2H lost from succinate are used to reduce the coenzyme FAD to FADH2.  Reaction 7: Hydration In reaction 7, hydration catalyzed by fumarase, water is added to the double bond of fumarate to yield malate, a secondary alcohol.  Reaction 8: Oxidation In reaction 8, oxidation catalyzed by malate dehydrogenase, ►the hydroxyl group in malate is oxidized to a carbonyl group, yielding oxaloacetate. ►oxidation provides hydrogen ions and electrons for the reduction of NAD+ to NADH and H+. Summary, Citric Acid Cycle Chapter Seven  Summary, Citric Acid Cycle ► Molecular oxygen molecules do not directly participate in citric acid cycle. However, the cycle operates only under aerobic conditions. ► Glycolysis has both an aerobic and an anaerobic mode, whereas the citric acid cycle is strictly aerobic.  Regulation of the Citric Acid Cycle ► The following enzymes: 1. pyruvate dehydrogenase 2. isocitrate dehydrogenase 3. α-ketoglutarate dehydrogenase ► are activated by high [ADP] (signs of ATP consumption) ► are inhibited by high [ATP], high [NADH] (signs that ATP is not being used) ► Citrate synthase is inhibited by high [ATP], high [NADH]  Electron Transport The reduced coenzymes NADH and FADH2 produced from glycolysis, oxidation of pyruvate, and the citric acid cycle are oxidized to provide the energy for the synthesis of ATP. In electron transport or the respiratory chain, ►hydrogen ions and electrons from NADH and FADH2 are passed from one electron acceptor or carrier to the next until they combine with oxygen to form H2O. ►energy released during electron transport is used to synthesize ATP from ADP and Pi during oxidative phosphorylation.  Electron Transport System In the electron transport system, ► there are five protein complexes, which are numbered I, II, III, IV, and V. ► two electron carriers, coenzyme Q and cytochrome c, attached to the inner membrane of the mitochondrion, carry electrons between these protein complexes bound to the inner membrane. Glycolysis, Citric Acid Cycle Results Electron Transport Chain  NADH to Complex I In complex I, ►electron transport begins when hydrogen ions and electrons are transferred from NADH to complex I. ►loss of hydrogen from NADH regenerates NAD+ to oxidize more substrates in oxidative pathways such as the citric acid cycle. ►hydrogen ions and electrons are transferred to the mobile electron carrier CoQ, forming CoQH2.  Complex I, Electron Transfer During electron transfer, complex I generates energy from electron transfer, ►H+ ions are pumped through complex I into the intermembrane space, producing a reservoir of H+ (hydrogen ion gradient). ►for every two electrons that pass from NADH to CoQ, 4H+ are pumped across the mitochondrial membrane, producing a charge separation on opposite sides of the membrane.  Coenzyme Q ► Coenzyme Q is also known as ubiquinone because of its widespread occurrence. ► CoQ is a mobile electron carrier that can accept one or two electrons. ► CoQ is lipid-soluble and can readily diffuse into the membrane. transports electrons from Complexes I and II to Complex III.  Complex II ► Complex II is the enzyme succinate dehydrogenase from the citric acid cycle. ► In complex II, CoQ obtains electrons directly from FADH2. This produces CoQH2 and regenerates the oxidized coenzyme FAD, which becomes available to oxidize more substrates. ► No H+ ions are pumped into the intermembrane space.  CoQH2 to Complex III ► The CoQH2 obtained from complex I and II will transfer electrons to Complex III. ► Two electrons are transferred from the mobile carrier CoQH2 to a series of iron-containing proteins called cytochromes inside complex III. ► Complex III generates energy from the electron transfer and pumps 4H+ from the matrix into the intermembrane space, increasing the hydrogen ion gradient.  Cytochrome c Cytochrome c ►contains Fe3+/Fe2+, which is reduced to Fe2+ and oxidized to Fe3+. ►is water-soluble and can only transfer one electron at a time. ► moves electrons from complex III to complex IV. ► For every 1 molecule of CoQH2, 2 molecules of cytochrome c is required.  Complex IV At complex IV, ►four electrons from four cytochrome c are passed to other electron carriers inside complex IV. ►electrons combine with hydrogen ions and oxygen (O2) to form two molecules of water. ►energy is used to pump H+ from the mitochondrial matrix into the intermembrane space, further increasing the hydrogen ion gradient.  Oxidative Phosphorylation ► Energy in electron transfer is coupled with the production of ATP in a process called oxidative phosphorylation. ► chemiosmotic model, which links the energy from electron transport drives the synthesis of ATP. ► Complexes I, III, and IV act as hydrogen ion pumps, producing a hydrogen ion gradient. ► The high [H+] in the intermembrane space wants to move H+ back to the matrix. ► The potential energy gained as they were moved against the gradient is now released and drives the oxidative phosphorylation through channel/enzyme: ATP Synthase  Oxidative Phosphorylation, ATP In the chemiosmotic model, ►H+ returns to the matrix by passing through a fifth protein complex in the inner membrane called ATP synthase (also called complex V). ►the flow of H+ from the intermembrane space through the ATP synthase generates energy that is used to synthesize ATP from ADP and Pi. This process of oxidative phosphorylation couples the energy from electron transport to the synthesis of ATP. Electron Transport and ATP Synthesis ► When NADH enters electron transport at complex I, the energy transferred can be used to synthesize 2.5 ATP. ► When FADH2 enters electron transport at complex II, it provides energy for the synthesis of 1.5 ATP. ► Current research indicates that the oxidation of one NADH yields 2.5 ATP and one FADH2 yields 1.5 ATP.  Problem Classify each as a product of the 1. CO2 A. citric acid cycle B. electron transport chain 2. FADH2 A. citric acid cycle B. electron transport chain 3. NAD+ A. citric acid cycle B. electron transport chain 4. NADH A. citric acid cycle B. electron transport chain 5. H2O A. citric acid cycle B. electron transport chain ATP from Oxidation of Glucose  Complete Oxidation of Glucose The complete oxidation of glucose to CO2 and H2O yields a maximum of 32 ATP.