CHAPTER 23: Metabolism & Energy Production

General, Organic, & Biological ChemistryJanice Gorzynski Smith

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

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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

Metabolism Definition

Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 3

•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.

Metabolism Overview

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

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Stage [1] – Digestion

Stage [2] – Formation of Acetyl CoA

Stage [3] – The Citric Acid Cycle

Stage [4] – Electron Transport Chain & Oxidative

Phosphorylation

Stage [1] – Digestion

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

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Metabolism

Carbohydrates

Proteins

Triacylglycerols

Metabolism Stage [2] – Formation of Acetyl CoA

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Metabolism Stage [3] – The Citric Acid Cycle

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•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.

Metabolism Stage [4] – Electron Transport Chain & Oxidative Phosphorylation

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•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

ATP Definition

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ATP Hydrolysis: Energy Released

Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 10

•Hydrolysis of ATP cleaves 1 phosphate group.

•This forms ADP and hydrogen phosphate (HPO42−),

releasing 7.3 kcal/mol of energy.

ATP Phosphorylation: Energy Absorbed

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•Phosphorylation is the reverse reaction, where a phosphate group is added to ADP, forming ATP requiring 7.3 kcal/mol of energy.

ATP Coupled Reactions

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•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.

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

Coenzymes Oxidation & Reduction

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Coenzymes Coenzyme A

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•Coenzyme A (HS-CoA) is neither an oxidizing nor a reducing agent.

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

•When the thioester bond is broken, 7.5 kcal/mol of energy is released.

Citric Acid Cycle

Overview

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•The citric acid cycle produces high-energy compounds for ATP synthesis in stage [4] of catabolism.

Citric Acid Cycle

Overview

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Citric Acid Cycle

Steps 1 - 4

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•Step [1] reacts acetyl CoA with oxaloacetate to form citrate, and it is catalyzed by citrate synthase.

•Step [2] isomerizes the 3o alcohol in citrate to the 2o alcohol in isocitrate; it is catalyzed by aconitase.

•Step [3] isocitrate loses CO2 in a decarboxylation reaction catalyzed by isocitrate dehydrogenase. Also, the 2o alcohol of isocitrate is oxidized by 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

Citric Acid Cycle

Steps 5 - 8

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•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; FADH2 is formed.

•Step [7], water is added across the C=C; this transforms fumarate into malate, which has a 2o alcohol.

•Step [8], the 2o 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].

Citric Acid Cycle

Overall Reaction

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The main function of the citric acid cycle is to produce reduced coenzymes (NADH and FADH2).

These molecules enter the electron transport chainand ultimately produce ATP.

Electron Transport

Definition

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•The electron transport chain is a multistep process using 4 enzyme complexes (I, II, III and IV) located along the mitochondrial inner membrane.

Electron Transport

Electron Transport Chain

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•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.

•These e− and H+ react with inhaled O2 to form water.

•The e− donated by the coenzymes are passed down from complex to complex in a series of redox reactions, which produces some energy.

ATP Synthesis Oxidative Phosphorylation

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•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 channel in 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.

ATP Synthesis Oxidative Phosphorylation

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•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

•Each NADH entering the electron transport chain produces enough energy to make 2.5 ATPs.

•Each FADH2 entering the electron transport chain produces enough energy to make 1.5 ATPs.

ATP Synthesis Oxidative Phosphorylation

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