Lecture Presentation Chapter 23 Metabolism and Energy Production Karen C Timberlake General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc Chapter 23 Metabolism and Energy Production Exercise physiologists work with athletes as well as patients who have been diagnosed with diabetes, heart disease, pulmonary disease, or other chronic disabilities or diseases Often these patients have been prescribed exercise as a form of treatment, and they have been referred to an exercise physiologist General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc Chapter 23 Readiness Core Chemistry Skills • Writing Equations for Hydrogenation, Hydration, and Polymerization (12.7) • Classifying Enzymes (20.2) • Identifying Important Coenzymes in Metabolism (22.2) • Identifying the Compounds in Glycolysis (22.4) General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc 23.1 The Citric Acid Cycle The citric acid cycle is a series of reactions that connects the intermediate acetyl CoA from the catabolic pathways in stage with electron transport and the synthesis of ATP in stage Learning Goal Describe the oxidation of acetyl CoA in the citric acid cycle General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc 23.1 The Citric Acid Cycle The citric acid cycle (stage 3) • operates under aerobic conditions • oxidizes the two-carbon acetyl group in acetyl CoA to CO2 • produces reduced coenzymes NADH and FADH2 • is named for the six-carbon citrate ion from citric acid (C6H8O7), a tricarboxylic acid, formed in the first reaction • is also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle Core Chemistry Skill Describing the Reactions in the Citric Acid Cycle General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc Citric Acid Cycle Overview In the citric acid cycle, • six carbons move through the citric acid cycle, producing oxaloacetate and 2CO2 • each turn contains four oxidation reactions producing the reduced coenzymes NADH and FADH2 • one GTP (converted to ATP in the cell) is produced during the citric acid cycle General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc Citric Acid Cycle Overview • In the citric acid cycle, eight reactions oxidize acetyl CoA from pyruvate or fatty acids, producing CO2 and the highenergy compounds FADH2, NADH, and GTP • Reactions involved in the citric acid cycle include condensation, dehydration, hydration, oxidation, reduction, and hydrolysis General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc Stages of Catabolism General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc Reaction 1: Formation of Citrate In the first reaction 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 General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc Reaction 2: Isomerization In reaction of the citric acid cycle, • citrate rearranges to isocitrate, a secondary alcohol • aconitase catalyzes the dehydration of citrate (tertiary alcohol) to yield cis-aconitate, followed by a hydration that forms isocitrate (secondary alcohol) General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc Solution Classify each as a product of the CO2 FADH2 NAD+ NADH H2O A citric acid cycle A citric acid cycle B electron transport chain A citric acid cycle B electron transport chain General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc 23.3 ATP Energy from Glucose The malate–aspartate shuttle transfers the energy stored in NADH to transporters that move from the cytosol into the mitochondrial matrix, where NADH is regenerated for use in electron transport Learning Goal Account for the ATP produced by the complete oxidation of glucose General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc ATP from Glycolysis The total ATP from complete oxidation of glucose is calculated by combining the ATP produced from • glycolysis (glucose produces ATP): five ATP from two NADH (malate–aspartate shuttle) and two ATP from direct phosphate transfer • the oxidation of pyruvate • the citric acid cycle • electron transport In glycolysis, the oxidation of glucose stores energy in two NADH molecules and two ATP molecules from direct phosphate transfer General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc Malate–Aspartate Shuttle Because glycolysis occurs in the cytosol, • the NADH produced cannot pass through the mitochondrial inner membrane • the hydrogen ions and electrons from NADH can be moved in and out of the mitochondria by a transporter, the malate–aspartate shuttle • malate dehydrogenase catalyzes the reaction of oxaloacetate and NADH to yield malate and NAD+ • a transporter binds the malate and carries it across the membrane into the matrix, where malate dehydrogenase oxidizes malate back to oxaloacetate General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc Malate–Aspartate Shuttle, ATP The oxidation to oxaloacetate provides hydrogen ions and electrons that are used to reduce NAD+ to NADH, which can now enter electron transport to synthesize ATP General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc Malate–Aspartate Shuttle, ATP Because the oxaloacetate produced in the matrix cannot cross the mitochondrial membrane, it • is converted back to aspartate; • moves out of the matrix back into the cytosol; and • undergoes transamination, which converts it to oxaloacetate The resulting NAD+ can participate again in glycolysis in the cytosol General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc ATP from Oxidation of Pyruvate Under aerobic conditions, pyruvate • enters the mitochondria • is oxidized to give acetyl CoA, CO2, and NADH Because glucose yields two pyruvate, • two NADH enter electron transport • their oxidation leads to the production of five ATP General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc ATP from Citric Acid Cycle The two acetyl CoA produced from two pyruvate enter the citric acid cycle Two acetyl CoA from one glucose produce a total of • six NADH; • two FADH2; and • two ATP In electron transport, six NADH produce 15 ATP, and two FADH2 produce ATP General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc ATP from Citric Acid Cycle In two turns of the citric acid cycle, a total of 20 ATP are produced NADH × 2.5 ATP/NADH = 15 ATP FADH2 × 1.5 ATP/FADH2 = ATP GTP × ATP/GTP Total two turns = ATP = 20 ATP The overall equation for the reaction of two acetyl CoA is General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc ATP from Oxidation of Glucose Core Chemistry Skill Calculating the ATP Produced from Glucose General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc Complete Oxidation of Glucose The complete oxidation of glucose to CO2 and H2O yields a maximum of 32 ATP General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc Chemistry Link to Health: Efficiency of ATP Production • In a laboratory calorimeter, mole of glucose produces 690 kcal C6H12O6 + 6O2 6CO2 + 6H2O + 690 kcal • To calculate the ATP energy produced in the mitochondria from glucose, we use the energy of the hydrolysis of ATP (7.3 kcal/mole of ATP) General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc Chemistry Link to Health: Efficiency of ATP Production Our cells are about 33% efficient in converting the total available chemical energy in glucose to ATP The remainder of the energy produced from glucose during the oxidation in our cells is lost as heat General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc Concept Map General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc ... C FADH2 D GTP General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc General, Organic, and Biological Chemistry: Structures of Life,... General, Organic, and Biological Chemistry: Structures of Life, 5/e Karen C Timberlake © 2016 Pearson Education, Inc Stages of Catabolism General, Organic, and Biological Chemistry: Structures of... 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 General, Organic, and Biological Chemistry: Structures