Chapter Twenty OneThe Generation of

Biochemical Energy

Outline• 21.1 Energy and Life• 21.2 Energy and Biochemical Reactions• 21.3 Cells and Their Structure• 21.4 An Overview of Metabolism and Energy Production• 21.5 Strategies of Metabolism: ATP and Energy Transfer• 21.6 Strategies of Metabolism: Metabolic Pathways and Coupled

Reactions• 21.7 Strategies of Metabolism: Oxidized and Reduced

Coenzymes• 21.8 The Citric Acid Cycle• 21.9 The Electron-Transport Chain and ATP Production• 21.10 Harmful Oxygen By-Products and Antioxidant Vitamins

Goals1. Provide an overview of the location of energy generation.2. Contrast exergonic and endergonic reactions in

metabolism.3. list the stages in catabolism and describe the role of each4. Explain the roles of ATP coupled reactions, and oxidized

and reduced coenzymes in metabolic pathways.5. Describe the events of the citric acid cycle (in general) and

explain its role in energy production.6. How is ATP generated in the final stage of catabolism? Be

able to describe in general the electron-transport chain, oxidative phosphorylation, and how they are coupled.

7. identify the highly reactive oxygen-containing products formed during metabolism and the enzymes and vitamins that counteract them.

Energy and Life1. Energy can be converted from one form to another, but

can’t be created or destroyed.-We need a constant supply of energy to power the external actions

we take as well as the internal activities of our bodies.

2. We can’t generate useful bodily energy by burning food:– Energy must be released gradually.– Energy must be stored in the body until used.– The rate of energy production and release must be finely

controlled.

3. We need just enough energy release to maintain a constant body temperature.-Energy must be available in forms other than heat.

Energy and Biochemical Reactions

The free energy of a reaction describes the effect of a combination of changes in disorder as well as loss or gain of heat energy.– Reactions in which the energy content of products is

less than that of reactants are said to have a negative value of free energy change• They are called exergonic can occur spontaneously.

– Reactions in which the energy content of products is greater than that of reactants are said to have a positive value of free energy change• They are called endergonic, and are thermodynamically

unfavorable ( do not occur spontaneously

Exergonic reactions Things to keep in mind • Chemical reactions proceed

according to the rules of thermodynamics

• In biochemistry as (as in every science, The law of conservation of energy holds firm.

• Nature favors an increase a release of free energy– Reactions that release free

energy are called exergonic

-DG = DH - TDS

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Energy and Biochemical Reactions

• Spontaneous reactions release free energy. DG = DH – TDS

• Favorable reactions, described as exergonic, are the source of our biochemical energy.

• Exergonic applies to the release of free energy, represented by a negative DG, Exothermic applies to the release of heat, represented by a negative DH .

DG = DH – TDS

Exergonic SpontaneousFree energy is released, DG is negative

Endergonic:

Non spontaneous reactionDG is positive

Energy and Life• Plants convert sunlight to potential energy stored in carbohydrate chemical

bonds (primarily in carbohydrates) • Animals use this energy for immediate needs, and store the rest in the

chemical bonds (primarily in fats)

• Is photosynthesis exergonic or Endergonic?

Endergonic Reactions Store Energy

In Photosynthesis, the sun provides the external energy for photosynthesis

Biochemical reactions that build molecules by making use of an energy “input” are part of anabolism

This is the reverse of the oxidation of glucose – a part of catabolism

Cells and Their Structure

• There are two main categories of cells: – prokaryotic cells, usually found in single celled

organisms including bacteria and blue-green algae– eukaryotic cells, found in some single-celled

organisms and all plants and animals.• Eukaryotic cells are about 1000 times larger than

bacterial cells, have a membrane enclosed nucleus that contains their DNA, and include several other kinds of internal structures known as organelles—small, functional units that perform specialized tasks.

Reduction of Free energy drives chemical and biochemical processesCatabolic breakdown of glucose: – The large molecule is broken down to carbon dioxide

and water (entropy increases)– Heat is released to the environment DH is negative –

enthalpy decreases– Entropy is a measure of how disorganized a system is– The chaos of the system increases: DS + – Change in free energy will be negative (a negative –

a positive will always be -):DG = DH – TDS

Exergonic (spontaineous reactions) driv Enderngonic processes

Catabolism-degradative, oxidative, energy yielding

Anabolism-synthetic, reductive, energy consuming

1. If DG is (-); the reaction is exergonic, (energy is released in the form of work); and the process is spontaneous

2. If DG is (+), the reaction is endergonic, (energy is absorbed in the form of work) and the reaction must be driven by external energy

What is taking place in terms on enthalpy, entropy and free energy?

DG =?

DG =?

Cell Components and Their Principal Function:

• Cilia - Movement of materials, i.e. mucus in lungs • Golgi apparatus - Cell membrane Synthesis• Rough endoplasmic reticulum - Protein synthesis • Nucleus - Replication of DNA• Ribosome - Protein synthesis• Microvilli - Absorption of extracellular substances• Lysosome - Removes pathogens/damaged organelles• Smooth endoplasmic reticulum - Lipid and

carbohydrate synthesis• Cell membrane - Governs entry and exit from cell

and deliver signals to interior of cell

Golgi apparatus - Cell membrane Synthesis

Rough endoplasmic reticulum - Protein synthesis

Ribosome - Protein synthesis

Smooth endoplasmic reticulum - Lipid and carbohydrate synthesis

Partnership

• Catabolism: Metabolic reaction pathways that break down food molecules and release biochemical energy.

• Anabolism: Metabolic reactions that build larger biological molecules from smaller pieces.

Cell Vocabulary

1. Cytoplasm: The region between the cell membrane and the nuclear membrane in a eukaryotic cell.

2. Cytosol: The fluid part of the cytoplasm surrounding the organelles within a cell.

3. Mitochondrion (plural, mitochondria):An egg-shaped organelle where small molecules are broken down to provide the energy for an organism.

4. Mitochondrial matrix: The space surrounded by the inner membrane of a mitochondrion.

5. Adenosine triphosphate (ATP): The principal energy-carrying molecule; removal of a phosphoryl group to give ADP releases free energy.

1. One of the most important types of organelles in prokaryotic cells is the mitochondrion, the “power plant” of the cell.

2. Mitochondria contain the enzymes of the electron transport chain, their own DNA, and enzymes that allow them to synthesize protein

Metabolism and Energy Production

– Together, all of the chemical reactions that take place in an organism constitute its metabolism.

• Catabolism: Metabolic reaction pathways that break down food molecules and release biochemical energy.

• Anabolism: Metabolic reactions that build larger biological molecules from smaller pieces.

Metabolic pathways may be linear, cyclic, or spiral.

Energy Production• The Breakdown of complex molecules to simpler molecules

with release of energy is termed catabolism.– Carbohydrates yields glucose and other sugars that can be oxidized

to acetyl groups that may be converted to carbon dioxide and water.– Proteins yields amino acids that may be further metabolized to

simpler molecules.– Triglycerides (fats and oils) are broken down into long chain fatty

acids. These may be broken down to acetyl groups and oxidized further to carbon dioxide and water.

• Acetyl groups from carbohydrates and fatty acids are attached to coenzyme A for transport through metabolic pathways.

• Energy produced in oxidative pathways is typically stored temporarily in molecules such asadenosine triphosphate (ATP)

Four stages of energy production

• Stage 1: Digestion• Stage 2: Acetyl-S-coenzyme A production• Stage 3: Citric acid cycle• Stage 4: ATP production

Stage 1: Digestion

• Enzymes convert the large molecules of lipids, carbohydrates, and proteins to smaller molecules.– Carbohydrates are broken down to glucose and other

sugars,– proteins are broken down to amino acids, and

triacylglycerols,– the lipids (fats and oils), are broken down to glycerol

plus long-chain carboxylic acids, the fatty acids.• These smaller molecules are transferred into the

blood for transport to cells throughout the body.

Stage 2: Acetyl-S-coenzyme A production

• The small molecules follow pathways that move their carbon atoms into two-carbon acetyl groups. – The acetyl groups are attached to coenzyme A by a sulfur bond

between fthe thiol group at the end of the coenzyme A molecule, and the carbonyl C atom of the acetyl group.

• Acetyl-SCoA, is the common intermediate in the breakdown of all classes of food.

Stage 3: Citric acid cycle

• Within mitochondria, • The acetyl-group carbon atoms are oxidized to the carbon

dioxide & exhaled.• Most of the energy released in the oxidation leaves the citric acid

cycle in the chemical bonds of reduced coenzymes.

Stage 4: ATP production

• Electrons from the reduced coenzymes are passed from molecule to molecule down an electron-transport chain.

• Along the way, energy is harnessed to produce more ATP.

• At the end of the process, electrons & along with hydrogen ions (from the reduced coenzymes)—combine with oxygen we breathe to produce water.

ATP and Energy Transfer• Removal of one phosphate group from ATP by

hydrolysis gives adenosine diphosphate (ADP).– Reaction is exergonic releasing chemical energy

from the phosphate bond.

ATP is an energy transporter

• The production of ATP from ADP requires an input of energy. – The energy is released wherever the reverse reaction

occurs.• Biochemical energy is gathered from exergonic reactions

that produce ATP. • The ATP then travels to where energy is needed, and ATP

hydrolysis releases the energy for whatever work must take place.

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Strategies of Metabolism: Metabolic Pathways and Coupled Reactions

• Not every individual step in every metabolic pathway is spontaneous.

• Energetically unfavorable reactions must be coupled with an energetically favorable reactions; so that the overall energy change for the two reactions is favorable.

• The principle of coupling must be put to use in the endergonic synthesis of ATP from ADP which has DG = +7.3 kcal/mol .

Coupled Reaction• Phosphoenolpyruvate is a molecule that has a higher

bond energy than ATP.• When the hydrolysis of phosphoenolpruvate is

coupled with the transfer of a phosphate to ATP, the overall energy change is favorable

Heat & Stored Potential EnergyThe energy provided by an exergonic reaction is either released as heat or stored as chemical potential energy in the bonds of products of the coupled endergonic reaction.

Strategies of Metabolism: Oxidized and Reduced Coenzymes• The net result of catabolism is the

oxidation of food to release energy.

• Many metabolic reactions are oxidation–reduction reactions.– Oxidation can be loss of electrons,

loss of hydrogen, or gain of oxygen.– Reduction can be gain of electrons,

gain of hydrogen, or loss of oxygen.• Oxidation and reduction always

occur together.

A steady supply of oxidizing and reducing agents must be available, so a few coenzymes continuously cycle between their oxidized and reduced forms.

• The oxidation of malate to oxaloacetate requires the removal of two H atoms to convert a secondary alcohol to a ketone.

• When considering enzyme-catalyzed redox reactions, it is important to recognize that an H atom is equivalent to a hydrogen ion, plus an electron.

• 2 H atoms removed in the oxidation of malate are equivalent to 2 H+ and 2 e- .

Secondary alcohol Keytoneoxidation

Reduction

• The reduction of NAD+ occurs by addition of H- to the ring in the nicotinamide part of the structure, where the two electrons of H- form a covalent bond.

• The second H atom removed from the oxidized substrate enters the surrounding solution as H+.

• The product of NAD+ reduction is often represented as NADH/ H+ to show that 2 H atoms have been removed from the reactant.

Flavin adenine dinucleotide, FAD, is reduced by the formation of covalent bonds to two H atoms to give FADH2 .It participates in the citric acid cycle.

Reduction can be gain of electrons, gain of hydrogen, or loss of oxygen

The Citric Acid Cycle

• Carbon atoms from the first two stages of catabolism are carried into the third stage as acetyl groups bonded to coenzyme A.

• The acetyl groups in acetyl-SCoA molecules are removed in an energy-releasing hydrolysis reaction.

• Oxidation of two carbons to give CO2 and transfer of energy to reduced coenzymes occurs in the citric acid cycle, also known as the tricarboxylic acid cycle (TCA) or Krebs cycle (after Hans Krebs, who unraveled its complexities in 1937).

► The citric acid cycle is a closed loop of reactions in which the product of the final step which has four carbon atoms, is the reactant in the first step.

• The net result of the citric acid cycle is:– Production of four reduced coenzyme molecules, 3

NADH and 1 FADH2

– Conversion of an acetyl group to two CO2 molecules– Production of one energy-rich molecule (GTP)

• ADP acts as an allosteric activator for the enzyme for Step 3. NADH acts as an inhibitor of the enzyme for Step 3.

• By such feedback mechanisms, the cycle is activated when energy is needed and inhibited when energy is in good supply.

• The eight steps of the citric acid cycle are shown in greater detail on the next slide.

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21.9 The Electron-Transport Chain and ATP Production

• At the conclusion of the citric acid cycle, the reduced coenzymes formed in the cycle are ready to donate their energy to making additional ATP

• Hydrogen and electrons from NADH and FADH2 enter the electron-transport chain at enzyme complexes I and II, respectively.

• The enzyme for Step 6 of the citric acid cycle is part of complex II. FADH2 produced there does not leave complex II. Instead it is immediately oxidized there by reaction with coenzyme Q.

• Following formation of the mobile coenzyme Q, reductions occur when electrons are transferred.

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• Electrons are passed from weaker to increasingly stronger oxidizing agents, with energy released at each transfer.

► Coenzyme Q is also known as ubiquinone because of its widespread occurrence and because its ring structure with the two ketone groups is a quinone.

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Other important electron acceptors are various cytochromes, which are proteins that contain heme groups in which the iron cycles between Fe+2 and Fe+3 and proteins with iron–sulfur groups in which the iron also cycles between Fe+2 and Fe+3 .

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H+ ions are released for transport through the inner membrane at complexes I, III, and IV. Some of these ions come from the reduced coenzymes.

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• The H+ concentration difference creates a potential energy difference across the two sides of the inner membrane (like the energy difference between water at the top and bottom of the waterfall).

• The maintenance of this concentration gradient across the membrane is crucial—it is the mechanism by which energy for ATP formation is made available.

• ATP synthase: The enzyme complex in the inner mitochondrial membrane at which H+ ions cross the membrane and ATP is synthesized from ADP.

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• Oxidative phosphorylation: The synthesis of ATP from ADP using energy released in the electron transport chain.

• Each of the enzyme complexes I–IV contains several electron carriers.

• In the last step of the chain, electrons combine with oxygen that we breathe and H+ ions from the surroundings to produce water.

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21.10 Harmful Oxygen By-Products and Antioxidant Vitamins

• More than 90% of the oxygen we breathe is used in electron transport– ATP synthesis reactions.

• In these and other oxygen-consuming redox reactions, the product may not be water, but one or more of three highly reactive species.

• The superoxide ion, ·O2- , and the hydroxyl free radical,

·OH, can grab an electron from a bond in another molecule, which results in breaking that bond. The third oxygen by-product is hydrogen peroxide, H2O2 , a relatively strong oxidizing agent.

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Conditions that can enhance production of these three reactive oxygen species are represented in the drawing below. Some causes are environmental, such as exposure to smog or radiation. Others are physiological, including aging and inflammation.

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• Our protection against harmful oxygen species is provided by superoxide dismutase and catalase, which are among the fastest-acting enzymes.

• These and other enzymes are active inside cells where oxygen by-products are constantly generated. It is estimated that 1 in 50 of the harmful oxygen species escapes destruction inside a cell.

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• Protection is also provided by the antioxidant vitamins E, C, and A , all of which disarm free radicals by bonding with them.

• Vitamin E is fat-soluble, and its major function is to protect cell membranes from potential damage.

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Chapter Summary• We derive energy by oxidation of food molecules

that contain energy captured by plants from sunlight. • The energy is released gradually in exergonic

reactions and is available to do work, to drive endergonic reactions, to provide heat, or to be stored until needed.

• Energy generation in eukaryotic cells takes place in mitochondria.

• Food molecules undergo catabolism to provide energy in four stages. – (1) digestion to form smaller molecules that can be

absorbed into cells

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Chapter Summary Contd.– (2) decomposition into two-carbon acetyl groups that

are bonded to coenzyme A in acetyl-SCoA– (3) reaction of the acetyl groups via the citric acid

cycle to generate reduced coenzymes and CO2– (4) electron transport and transfer of the energy of

the reduced coenzymes from the citric acid cycle to our principal energy transporter, ATP.

• ADP is phosphorylated to give ATP. Where energy must be expended, it is released by removal of a phosphoryl group from ATP to give back ADP.

• An otherwise “uphill” reaction in a metabolic pathway is driven by coupling with an exergonic, “downhill” reaction that provides enough energy so that their combined outcome is exergonic.

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Chapter Summary Contd.• The oxidizing and reducing agents needed by the

many redox reactions of metabolism are coenzymes that constantly cycle between their oxidized and reduced forms

• The citric acid cycle is a cyclic pathway of eight reactions.

• Along the way, four reduced coenzyme molecules and one molecule of ATP are produced for each acetyl group oxidized.

• The reduced coenzymes carry energy for the subsequent production of additional ATP.

• The cycle is activated when energy is in short supply and inhibited when energy is in good supply.

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Chapter Summary Contd.• Electrons and H+ ions from NADH and FADH2

are transferred to coenzyme Q.• Then, the electrons and H+ ions proceed

independently, the electrons gradually giving up their energy to the transport of H+ ions across the inner mitochondrial membrane to maintain different concentrations on opposite sides of the membrane.

• The H+ ions return to the matrix by passing through ATP synthase, where the energy they release is used to convert ADP to ATP.

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Chapter Summary Contd.

• Harmful by-products of oxygen-consuming reactions are the hydroxyl free radical, superoxide ion (also a free radical), and hydrogen peroxide.

• These reactive species damage other molecules by breaking bonds.

• Superoxide dismutase and catalase are enzymes that disarm these oxygen by-products.

• Vitamins E, C, and A are also antioxidants.

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Key Words

•Acetyl-S-coenzyme A (acetyl-SCoA)•Adenosine triphosphate (ATP)•Anabolism•ATP synthase•Catabolism•Citric acid cycle•Cytoplasm•Cytosol

•Electron-transport chain•Endergonic•Exergonic•Guanosine diphosphate (GDP)•Guanosine triphosphate (GTP)•Mitochondrial matrix•Mitochondrion•Oxidative phosphorylation

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End of Chapter Twenty One