CHAPTER 23: Metabolism & Energy Production General, Organic, & Biological Chemistry

1. CHAPTER 23: Metabolism & Energy Production General, Organic, & Biological Chemistry Janice Gorzynski Smith

2. CHAPTER 23: Metabolism & Energy Production • Learning Objectives: • Stages of Metabolism • ATP: structure, hydrolysis, & formation • Coupling reactions • Coenzymes • NAD+ & NADH • FAD & FADH2 • Coenzyme A • Citric Acid Cycle: all 8 steps • Electron Transport Chain • ATP synthesis by Oxidative Phosphorylation • CH 23 Homework: • End of Chapter problems: 20, 22, 24, 26, 28, 32, 34, 36, 40, 42, 46, 48, 50, 52, 56, 60, 64, 74 Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

3. Metabolism Definition • Metabolism is the sum of all the chemical reactions that take place in an organism. • Catabolism is the breakdown of large molecules into smaller ones; energy is generally released during catabolism. Anabolism is the synthesis of large molecules from smaller ones; energy is generally absorbed during anabolism. • Often, the process is a series of consecutive reactions called a metabolic pathway, which can be linear or cyclic. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

4. Metabolism Overview Stage [1] – Digestion Stage [2] – Formation of Acetyl CoA Stage [3] – The Citric Acid Cycle Stage [4] – Electron Transport Chain & Oxidative Phosphorylation Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

5. Metabolism Stage [1] – Digestion Carbohydrates Proteins Triacylglycerols Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

6. Metabolism Stage [2] – Formation of Acetyl CoA Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

7. Metabolism Stage [3] – The Citric Acid Cycle • The citric acid cycle is based in the mitochondria, where the acetyl CoA is oxidized to CO2. • The cycle also produces energy stored as a nucleoside triphosphate and the reduced coenzymes. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

8. Metabolism Stage [4] – Electron Transport Chain & Oxidative Phosphorylation • Within the mitochondria, the electron transport chain and oxidative phosphorylation produce ATP (adenosine 5’-triphosphate). • ATP is the primary energy-carrying molecule in the body Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

9. ATP Definition Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

10. ATP Hydrolysis: Energy Released • Hydrolysis of ATP cleaves 1 phosphate group. • This forms ADP and hydrogen phosphate (HPO42−), • releasing 7.3 kcal/molof energy. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

11. ATP Phosphorylation: Energy Absorbed • Phosphorylation is the reverse reaction, where • a phosphate groupis added to ADP, forming ATP • requiring 7.3 kcal/molof energy. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

12. ATP Coupled Reactions • Coupled reactions are pairs of reactions that occur together. • The energy released by one reaction is absorbed by the otherreaction. • Coupling an energetically unfavorable reaction with a favorable one that releases more energy than the amount required is common in biological reactions. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

13. Coenzymes Oxidation & Reduction Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

14. Coenzymes Coenzyme A • Coenzyme A(HS-CoA) is neither an oxidizing • nor a reducing agent. • When the thioester bond is broken, 7.5 kcal/mol • of energy is released. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

15. Citric Acid Cycle Overview • The citric acid cycle produces high-energy compounds for ATP synthesisin stage [4] of catabolism. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

16. Citric Acid Cycle Overview Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

17. Citric Acid Cycle Steps 1 - 4 • Step [1] reacts acetyl CoA with oxaloacetateto form citrate, and it is catalyzed by citrate synthase. • Step [2] isomerizes the 3oalcohol in citrate to the 2o alcohol in isocitrate; it is catalyzed by aconitase. • Step [3] isocitrateloses CO2in a decarboxylation reaction catalyzed by isocitratedehydrogenase. Also, the 2o alcohol of isocitrateis oxidizedby the oxidizing agent NAD+ to form the ketone a-ketoglutarate and NADH • Step [4] releases another CO2 with the oxidation of a-ketoglutarate by NAD+ in the presence of coenzyme A to form succinyl CoA and NADH. Catalyzed by a-ketoglutarate dehydrogenase Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

18. Citric Acid Cycle Steps 5 - 8 • Step [5] the thioester bond of succinylCoA is hydrolyzed to form succinate, releasing energy that converts GDP to GTP. • Step [6] succinate is converted to fumaratewith FAD and succinate dehydrogenase; FADH2 is formed. • Step [7], water is added across the C=C; this transforms fumarate into malate, which has a 2oalcohol. • Step [8], the 2oalcohol of malate is oxidizedby NAD+ to form the ketone portion of oxaloacetate and NADH. The product of step [8] is the starting material for step [1]. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

19. Citric Acid Cycle Overall Reaction The main function of the citric acid cycle is to produce reduced coenzymes (NADH and FADH2). These molecules enter the electron transport chain and ultimately produce ATP. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

20. Electron Transport Definition • The electron transport chain is a multistep • process using 4 enzyme complexes (I, II, III and IV) • located along the mitochondrial inner membrane. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

21. Electron Transport Electron Transport Chain • The reduced coenzymes (NADH and FADH2) are • reducing agents, and can donate e− when oxidized. • NADH is oxidized to NAD+ and FADH2 is oxidized • to FAD when they enter the electron transport • chain. • The e− donated by the coenzymes are passed • down from complex to complex in a series of • redox reactions, which produces some energy. • These e− and H+react with inhaled O2to form water. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

22. ATP Synthesis 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 inter membrane space becomes higher than that inside the matrix creating a potential energy gradient. • To return to the matrix, H+ ions travel through a • channelin the ATP synthase enzyme (catalyzes phosphorylation of ADP to ATP). • The energy released as the H+ ions return to the • matrix is the energy stored in the ATP molecule. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

23. ATP Synthesis Oxidative Phosphorylation • Each NADH entering the electron transport chain • produces enough energy to make 2.5 ATPs. • Each FADH2entering the electron transport chain • produces enough energy to make 1.5 ATPs. • The citric acid cycle produces overall: 3 NADH x 2.5 ATP = 7.5 ATP 1 FADH2 x 1.5 ATP = 1.5 ATP 1 GTP = 1 ATP 10 ATP Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.

24. ATP Synthesis Oxidative Phosphorylation Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed.