Chapter Chapter Twenty ThreeTwenty Three

Biochemical Energy Production

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Metabolism

• The sum total of all the biochemical reactions that take place in a living organism

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Metabolic Reactions occur in specific sites within cells

Typical animal cell• Nucleus

– Chromosomes in the nucleus contain genetic material

• Cytoplasm is material between nucleus and cell membrane

• Mitochondria are where energy-producing reactions occur

Cell Structure

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(a) Representation of a mitochondria. (b) micrograph of a mitochondria crista.

Biochemical Energy Production

© R. Bhatnagar / Visuals Unlimited

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• Energy is released as food is oxidized• Used to form ATP from ADP and Pi

ADP + Pi + Energy ATP • In cells, energy is provided by the hydrolysis of ATP (31

kJ/mole of ATP)

ATP ADP + Pi + Energy

ATP

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Biochemical Energy Production

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High-Energy Phosphate Compounds

• Phosphate containing compounds that have a greater free energy of hydrolysis than that of a typical compound– The energy of hydrolysis is large because of strong

repulsive forces between electronegative atoms– Enough energy is released by their hydrolysis to

compensate for the energy needed for ATP production

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Major Coenzymes in Metabolic Reactions

• NAD+/NADH

• FAD/FADH2

• Coenzyme A (CoA-SH)

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(a) Flavin adenine nucleotide (b) nicotinamide adenine dinucleotide

Major Coenzymes in Metabolic Reactions

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Major Coenzymes in Metabolic Reactions

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Structural formula for coenzyme A CoA-SH

Biochemical Energy Production

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Coenzyme NAD+

• In cells, the oxidation of compounds provides 2H as 2H+ and 2e- that reduce coenzymes

• NAD+ (nicotinamide adenine dinucleotide) participates in reactions that produce a carbon-oxygen double bond (C=O)Oxidation

CH3-CH2-OH CH3-CHO + 2H+ + 2e-

ReductionNAD+ + 2H+ + 2e- NADH + H+

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Coenzyme FAD

• FAD participates in reactions that produce a carbon-carbon double bond (C=C)

Oxidation

-CH2-CH2- -CH=CH- + 2H+ + 2e-

Reduction

FAD + 2H+ + 2e- FADH2

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Classification of metabolic intermediate compounds in terms of function.

Biochemical Energy Production

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Free Energies of

Hydrolysis of

Phosphate

Containing

Compounds

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Hans Adolf Krebs received the Nobel Prize in medicine.

Biochemical Energy Production

Hulton Archive / Getty Images

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Stages of Metabolism

Catabolic reactions are organized as stages• In Stage 1, digestion breaks down large molecules

into smaller ones that enter the bloodstream.• In Stage 2, molecules in the cells are broken down

to two- and three-carbon compounds

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Digestion is the first step of catabolism

• Carbohydrates glucose, fructose, galactose

• Proteins amino acids

• Lipids glycerol fatty acids

Digestion of Foods

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Stages of Metabolism

• In Stage 3, compounds are oxidized in the citric acid cycle to provide NADH and FADH2 molecules (reduced forms of coenzymes)

• In Stage 4, NADH and FADH2 are oxidized in order to provide energy for the production of ATP

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Citric Acid Cycle

The citric acid cycle:• Operates under aerobic conditions only• Oxidizes the two-carbon acetyl group in acetyl

CoA to CO2

• Produces reduced coenzymes NADH and FADH2 and one ATP directly

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Reaction 1: Formation of Citrate

• Oxaloacetate combines with the two carbon acetyl group to form citrate

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Reaction 2: Formation of Isocitrate

• Citrate isomerizes to isocitrate• The tertiary –OH group in citrate is converted to

a secondary –OH group that can be oxidized

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Reaction 3: Oxidative Decarboxylation (1)

• A decarboxylation removes a carbon as CO2 from isocitrate.

• The –OH group is oxidized to a ketone, releasing H+ and 2e- that form reduced coenzyme NADH

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Reaction 4: Oxidative Decarboxylation (2)

• In a second decarboxylation, a carbon is removed as CO2 from a-ketoglutarate

• The 4-carbon compound bonds to coenzyme A, providing H+ and 2e- to form NADH

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Reaction 5: Hydrolysis

• The hydrolysis of the thioester bond releases energy to add phosphate to GDP and form GTP, a high energy compound

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Reaction 6: Dehyrogenation

• In this oxidation, two H are removed from succinate to form a double bond in fumarate

• FAD is reduced to FADH2

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Reaction 7: Hydration of Fumarate

• Water is added to the double bond in fumarate to form malate

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Reaction 8: Dehyrogenation

• Another oxidation forms a C=O bond• The hydrogens from the oxidation form NADH + H+

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Summary of Products in the Citric Acid Cycle

In the citric acid cycle:• Oxaloacetate bonds with an acetyl group to form

citrate• Two decarboxylations remove two carbons as

2CO2

• Four oxidations provide hydrogen for 3NADH and one FADH2

• A direct phosphorylation forms GTP

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Overall Chemical Reaction for the Citric Acid Cycle

Acetyl CoA + 3NAD+ + FAD

+ GDP + Pi + 2H2O

2CO2 + 3NADH + 2H+ + FADH2

+ HS-CoA + GTP

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Regulation of Citric Acid Cycle

• Low levels of ATP stimulate the formation of acetyl CoA for the citric acid cycle

• High ATP and NADH levels decrease the formation of acetyl CoA and slow down the citric acid cycle

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Regulation of Citric Acid Cycle

The citric acid cycle:• Increases its reaction rate when low levels of ATP

or NAD+ activate isocitrate dehydrogenase• Slows when high levels of ATP or NADH inhibit

citrate synthetase (first step in cycle)

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Electron Carriers

Electron carriers:• Accept hydrogen and electrons from the reduced

coenzymes NADH and FADH2

• Are oxidized and reduced to provide energy for the synthesis of ATP

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Oxidation-Reduction

• Electron carriers are continuously oxidized and reduced as hydrogen and/or electrons are transferred from one to the next

Electron carrier A (reduced)

Electron carrier A (oxidized)

Electron carrier B (oxidized)

Electron carrier B (reduced)

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Electron Transport Chain

• A series of biochemical reactions in which electrons and hydrogen ions from NADH and FADH2 are passed to intermediate electron carriers and then ultimately react with molecular oxygen to produce water

• Most of the enzymes for the Electron Transport Chain are found in the inner mitochondrial membrane (found in the order in which they are needed)

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Biochemical Energy Production

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(a) The oxidized form and reduced form of the electron carrier flavin mononucleotide. (b) The oxidized form and reduced form of the electron carrier coenzyme Q.

Biochemical Energy Production

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(a) CoQH2 carries electrons from both complexes I and II to complex III. (b) NADH is the substrate for the complex I and FADH2 is the substrate for complex II.

Biochemical Energy Production

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Electron movement through Complex III is initiated by the electron carrier CoQH2.

Biochemical Energy Production

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The electron-transfer pathway through Complex IV.

Biochemical Energy Production

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Protein complexes I, III, and IV also act as proton pumps.

Biochemical Energy Production

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Chemiosmotic Model

In the chemiosmotic model:• Complexes I, III, and IV pump protons into the

intermembrane space, creating a proton gradient.• Protons must pass through ATP synthase to return

to the matrix• The flow of protons through ATP synthase

provides the energy for ATP synthesis (oxidative phosphorylation)– ADP + Pi + Energy ATP

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ATP Synthase

ATP Synthase has two portions:• Protons flow back to the matrix through a channel

in the F0 complex.• Proton flow provides the energy that drives ATP

synthesis by the F1 complex

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ATP Production for the Common Metabolic Pathway

• For every mole of NADH oxidized in the ETC, 2.5 moles of ATP are formed– 3 formed in one turn of citric acid cycle (7.5 ATP)

• For every mole of FADH2 oxidized in the ETC, 1.5 moles of ATP are formed– 1 formed in one turn of citric acid cycle (1.5 ATP)

• GTP is the equivalent of ATP– 1 formed in one turn of the citric acid cycle (1 ATP)

10 ATP Overall!!!

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The interconversion of ATP and ADP is the principal medium for energy exchange in the biochemical processes.

Biochemical Energy Production