Metabolism & Energy Production

Chapter 23 Lecture Outline

• Prepared by Andrea Leonard, University of Louisiana at Lafayette
• Copyright 2022 © McGraw Hill LLC. All rights reserved.
• No reproduction or distribution without prior written consent.

23.1 Introduction

• Metabolism: The sum of all chemical reactions in an organism.
• Catabolism:
  • The breakdown of large molecules into smaller ones.
  • Energy is generally released during catabolism.
• Anabolism:
  • The synthesis of large molecules from smaller ones.
  • Energy is generally absorbed during anabolism.
• Metabolic Pathway: A series of consecutive reactions (linear or cyclic).
• Linear Pathway: Generates a final product different from any of the reactants.
• Cyclic Pathway: Regenerates the first reactant.
• Energy Production: Occurs in the mitochondria.
  • Mitochondria: Organelles within the cytoplasm of a cell.
    • Contain an outer and inner membrane with folds.
    • Intermembrane Space: Area between the two membranes.
    • Matrix: Area enclosed by the inner membrane, where energy production occurs.

23.2 An Overview of Metabolism

A. Stage [1]—Digestion

• The catabolism of food begins with digestion.
• Catalyzed by enzymes in saliva, stomach, and small intestines.
• Carbohydrates: Hydrolyzed into monosaccharides.
  • Begins with amylase enzymes in saliva.
  • Continues in the small intestine.
• Proteins: Digestion begins in the stomach.
  • Stomach acid denatures the protein.
  • Pepsin cleaves the protein into smaller peptides.
  • In the small intestines, trypsin and chymotrypsin cleave peptides into amino acids.
• Triacylglycerols:
  • Emulsified by bile secreted by the liver.
  • Hydrolyzed by lipases in the small intestines into 3 fatty acids and a glycerol backbone.

B. Stage [2]—Formation of Acetyl CoA

• Monosaccharides, amino acids, and fatty acids are degraded into acetyl groups.
• Acetyl groups are bonded to coenzyme A, forming acetyl-CoA.

C. Stage [3]—The Citric Acid Cycle

• Occurs in the mitochondria.
• Acetyl CoA is oxidized to CO_2.
• Produces energy stored as a nucleoside triphosphate and reduced coenzymes.

D. Stage [4]—The Electron Transport Chain and Oxidative Phosphorylation

• Occurs within the mitochondria.
• Produces ATP (adenosine 5’-triphosphate).
• ATP is the primary energy-carrying molecule in the body.

23.3 ATP and Energy Production

A. General Features of ATP Hydrolysis

• Hydrolysis of ATP cleaves one phosphate group.
• Forms ADP and hydrogen phosphate.
• Releases 7.3 kcal/mol of energy.

A. General Features of ATP Phosphorylation

• Phosphorylation is the reverse reaction.
• A phosphate group is added to ADP, forming ATP.
• Requires 7.3 kcal/mol of energy.
• Any process (walking, running, breathing) is fueled by the release of energy when ATP is hydrolyzed to ADP.
• Energy is absorbed and stored in ATP when synthesized from ADP.

B. Coupled Reactions in Metabolic Pathways

• Coupled reactions are pairs of reactions that occur together.
• The energy released by one reaction is absorbed by the other reaction.
• Coupling an energetically unfavorable reaction with a favorable one that releases more energy than the amount required is common in biological reactions.
• The hydrolysis of ATP provides the energy for the phosphorylation of glucose.

C. Focus on the Human Body

• Creatine: An amino acid byproduct taken by athletes as a supplement.
• Stored in muscle tissue as creatine phosphate, a high-energy molecule.
• Creatine phosphate hydrolysis provides energy for ADP phosphorylation to produce ATP.
• Provides high levels of energy for short bursts of intense activity.

23.4 Coenzymes in Metabolism

A. Coenzymes and NADH

• Oxidation: Results in a loss of electrons, loss of hydrogen, or gain of oxygen.
• Reduction: Results in a gain of electrons, gain of hydrogen, or loss of oxygen.
• A coenzyme acting as an oxidizing agent causes an oxidation reaction to occur, so the coenzyme is reduced; it gains H+ and e−.
• A coenzyme acting as a reducing agent causes a reduction reaction to occur, so the coenzyme is oxidized; it loses H+ and e−.
• Coenzyme NAD+ (nicotinamide adenine dinucleotide) is an oxidizing agent.
• After gaining H+ and 2e−, the reduced form of NAD+ is NADH.

B. Coenzymes FAD and FAD

• FAD (flavin adenine dinucleotide) is an oxidizing agent.
• After gaining 2H+ and 2e−, the reduced form of FAD is FADH2.
• FAD is synthesized in cells from vitamin riboflavin.
  • Riboflavin is a yellow, water-soluble vitamin obtained in the diet.
  • Excess riboflavin is excreted in the urine, giving it a bright yellow appearance.

C. Coenzyme A

• Coenzyme A (HS-CoA) is neither an oxidizing nor a reducing agent.
• When an acetyl group reacts with the sulfhydryl end of coenzyme A, the thioester acetyl CoA is formed.
• When the thioester bond is broken, 7.5 kcal/mol of energy is released.

23.5 The Citric Acid Cycle

• The citric acid cycle is a cyclic metabolic pathway.
• Begins with the addition of acetyl CoA to a four-carbon substrate.
• The cycle ends when the same four-carbon substrate is formed as a product eight steps later.
• The citric acid cycle produces high-energy compounds for ATP synthesis in stage [4] of catabolism.

A. Overview of the Citric Acid Cycle

• Begins when 2 C’s of acetyl CoA react with a four-carbon substrate to form a six-carbon product (step [1]).
• 2 C atoms are sequentially removed to form 2 CO_2 molecules (steps [3] and [4]).
• 4 molecules of reduced coenzymes (3 NADH’s and 1 FADH_2) are formed (steps [3], [4], [6], and [8]).
• 1 mole of GTP is made in step [5]; GTP is similar to ATP.

B. Specific Steps of the Citric Acid Cycle

• Step [1]: Acetyl CoA reacts with oxaloacetate to form citrate; catalyzed by citrate synthase.
• Step [2]: Isomerizes the ata-alcohol in citrate to the ata-alcohol in isocitrate; catalyzed by aconitase.
• Step [3]: Isocitrate loses CO_2 in a decarboxylation reaction catalyzed by isocitrate dehydrogenase. The ata-alcohol of isocitrate is oxidized by the oxidizing agent NAD^+ to form the ketone ata and NADH.
• Step [4]: Releases another CO_2 with the oxidation of ata by NAD^+ in the presence of coenzyme A to form succinyl CoA and NADH. This step is catalyzed by dehydrogenase.
• Step [5]: The thioester bond of succinyl CoA is hydrolyzed to form succinate, releasing energy that converts GDP to GTP.
• Step [6]: Succinate is converted to fumarate with FAD and succinate dehydrogenase; FADH_2 is formed.
• Step [7]: Water is added across the ata, transforming fumarate into malate, which has a ata-alcohol.
• Step [8]: The ata-alcohol of malate is oxidized by NAD^+ to form the ketone portion of oxaloacetate and NADH. The product of step [8] is the starting material for step [1].
• The overall citric acid cycle yields:
  • 2 CO_2 molecules.
  • 3 NADH and 1 FADH_2 molecules.
  • 1 GTP molecule.
• The main function of the citric acid cycle is to produce reduced coenzymes (NADH and FADH_2).
• These molecules enter the electron transport chain and ultimately produce ATP.

23.6 The Electron Transport Chain

A. The Electron Transport Chain

• A multistep process using 4 enzyme complexes (I, II, III, and IV) located along the mitochondrial inner membrane.
• The reduced coenzymes (NADH and FADH_2) are reducing agents and can donate H+ and e− when oxidized.
• NADH is oxidized to NAD^+ and FADH_2 is oxidized to FAD when they enter the electron transport chain.
• The H+ and e− donated by the coenzymes are passed down from complex to complex in a series of redox reactions, which produces some energy.
• These H+, e−, and inhaled O_2 react to form water.
• This process is aerobic because of the use of O_2.

B. ATP Synthesis by Oxidative Phosphorylation

• The electron transport chain provides the energy to pump H+ ions across the inner membrane of the mitochondria.
• The concentration of H+ ions in the intermembrane space becomes higher than that inside the matrix.
• This creates a potential energy gradient.
• To return to the matrix, H+ ions travel through a channel in the ATP synthase enzyme.
• ATP synthase is the enzyme that catalyzes the phosphorylation of ADP into ATP.
• The energy released as the H+ ions return to the matrix is the energy stored in the ATP molecule.
• It is called oxidative phosphorylation because the energy used to transfer the phosphate group results from the oxidation of the coenzymes.

C. ATP Yield from Oxidative Phosphorylation

• Each NADH entering the electron transport chain produces enough energy to make 2.5 ATPs.
• Each FADH_2 entering the electron transport chain produces enough energy to make 1.5 ATPs.
• The citric acid cycle produces overall: 10 ATP

23.7 Focus on Health & Medicine: Hydrogen Cyanide

• If any one step of the electron transport chain or oxidative phosphorylation is disrupted, an organism cannot survive.
• Hydrogen cyanide (HCN) produces CN−, which irreversibly binds to the ata portion of the cytochrome oxidase.
• Cytochrome oxidase is a key enzyme of complex IV of the electron transport chain.
• This prevents the O2 from being reduced to H2O, halting the electron transport chain and energy production.
• ATP is not synthesized, and cell death occurs.
• Amygdalin is present in the seeds and pits of apricots, peaches, and wild cherries.
• HCN is produced by hydrolysis.