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1

18.1 Metabolism and ATP Energy

Chapter 18 Metabolic Pathways and Energy Production

2

Metabolism involves • catabolic reactions

that break down large, complex molecules to provide energy and smaller molecules.

• anabolic reactions that use ATP energy to build larger molecules.

Metabolism

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Stages of Metabolism

Catabolic reactions are organized as • Stage 1: Digestion and hydrolysis break down

large molecules to smaller ones that enter the bloodstream.

• Stage 2: Degradation break down molecules to two- and three-carbon compounds. • Stage 3: Oxidation of small molecules in the citric

acid cycle and electron transport provides ATP energy.

4

Stages of Metabolism

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Cell Structure and Metabolism

Metabolic reactions occur in specific sites within cells.

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6

Cell Components and Function

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ATP and Energy

In the body, energy is stored as adenosine triphosphate (ATP).

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Hydrolysis of ATP

• The hydrolysis of ATP to ADP releases 7.3 kcal. ATP ADP + Pi + 7.3 kcal

9

ATP and Muscle Contraction

Muscle fibers • contain the protein fibers actin and myosin.

• contract (slide closer together) when a nerve impulse increases Ca2+.

• obtain the energy for contraction from the hydrolysis of ATP.

• return to the relaxed position as Ca2+ and ATP decrease.

10

ATP and Muscle Contraction

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Learning Check

Match the following: 1) ATP 2) ADP + Pi A. used in anabolic reactions B. the energy-storage molecule C. coupled with energy-requiring reactions D. hydrolysis products

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Solution

Match the following: 1) ATP 2) ADP + Pi A. 1 used in anabolic reactions B. 1 the energy-storage molecule C. 1 coupled with energy-requiring reactions D. 2 hydrolysis products

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18.2 Digestion of foods

Chapter 18 Metabolic Pathways and Energy Production

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In Stage 1, the carbohydrates • begin digestion in the mouth, where salivary amylase

breaks down polysaccharides to smaller polysaccharides (dextrins), maltose, and some glucose.

• continue digestion in the small intestine, where pancreatic amylase hydrolyzes dextrins to maltose and glucose.

• maltose, lactose, and sucrose are hydrolyzed to monosaccharides, mostly glucose, which enter the bloodstream for transport to the cells.

Stage 1: Digestion of Carbohydrates

Carbohydrate Digestion

15

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Digestion of Fats

In Stage 1, the digestion of fats (triacylglycerols)

• begins in the small intestine, where bile salts break fat globules into smaller particles called micelles.

• uses pancreatic lipases to hydrolyze ester bonds, forming glycerol and fatty acids.

• ends as fatty acids bind with proteins for transport to the cells of the heart, muscle, and adipose tissues.

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Digestion of Triacylglycerols

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Digestion of Proteins

In Stage 1, the digestion of proteins

• begins in the stomach, where HCl in stomach acid activates pepsin to hydrolyze peptide bonds.

• continues in the small intestine, where trypsin and chymotrypsin hydrolyze peptides to amino acids.

• ends as amino acids enter the bloodstream for transport to cells.

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Digestion of Proteins

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Learning Check

Match the end products of digestion with the types of food. 1) amino acids 2) fatty acids and glycerol 3) glucose A. fats B. proteins C. carbohydrates

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Solution

Match the end products of digestion with the types of food. A. fats 2) fatty acids and glycerol B. proteins 1) amino acids C. carbohydrates 3) glucose

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Chapter 18 Metabolic Pathways and Energy Production

18.3 Important Coenzymes in

Metabolic Pathways

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Oxidation and Reduction

To extract energy from foods • oxidation reactions involve a loss of 2 H (2H+ and 2 e–). compound oxidized compound + 2 H • reduction reactions require coenzymes that pick up 2 H. coenzyme + 2H reduced coenzyme

24

Coenzyme NAD+

NAD+ (nicotinamide adenine dinucleotide) • participates in reactions that produce a carbon-oxygen double

bond (C=O). • is reduced when an oxidation provides 2H+ and 2 e–. Oxidation O || CH3—CH2—OH CH3—C—H + 2H+ + 2 e– Reduction NAD+ + 2H+ + 2 e– NADH + H+

25

Structure of Coenzyme NAD+

• contains ADP, ribose, and nicotinamide.

• is reduced to NADH when NAD+ accepts 2H+ and 2 e–.

NAD+ (nicotinamide adenine dinucleotide)

26

Coenzyme FAD

FAD (flavin adenine dinucleotide) • participates in reactions that produce a carbon-carbon

double bond (C=C). • is reduced to FADH2. Oxidation —CH2—CH2— —CH=CH— + 2H+ + 2 e– Reduction FAD + 2H+ + 2 e– FADH2

27

Structure of Coenzyme FAD

FAD (flavin adenine dinucleotide) • contains ADP

and riboflavin (vitamin B2).

• is reduced to FADH2 when flavin accepts 2H+ and 2 e–.

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Coenzyme A

Coenzyme A (CoA) activates acyl groups such as the two carbon acetyl group for transfer. O O || || CH3—C— + HS—CoA CH3—C—S—CoA Acetyl group Acetyl CoA

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Structure of Coenzyme A

Coenzyme A (CoA) contains • pantothenic acid (Vitamin B3). • ADP. • aminoethanethiol.

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Learning Check

Match the following. 1) NAD+ 2) FAD 3) NADH + H+

4) FADH2 5) Coenzyme A A. coenzyme used in oxidation of carbon-oxygen bonds B. reduced form of flavin adenine dinucleotide C. used to transfer acetyl groups D. oxidized form of flavin adenine dinucleotide E. the coenzyme after C=O bond formation

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Solution

Match the following. 1) NAD+ 2) FAD 3) NADH + H+

4) FADH2 5) Coenzyme A A. 1 coenzyme used in oxidation of carbon-oxygen bonds B. 4 reduced form of flavin adenine dinucleotide C. 5 used to transfer acetyl groups D. 2 oxidized form of flavin adenine dinucleotide E. 3 the coenzyme after C=O bond formation

32

Chapter 18 Metabolic Pathways and Energy Production

18.4 Glycolysis Oxidation

of Glucose

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Stage 2: Glycolysis

Stage 2: Glycolysis • is a metabolic

pathway that uses glucose, a digestion product.

• degrades six-carbon glucose molecules to three-carbon pyruvate molecules.

• is an anaerobic (no oxygen) process.

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34

Glycolysis: Energy-Investment

In reactions 1-5 of glycolysis, • energy is required to add phosphate groups to glucose. • glucose is converted to two three-carbon molecules.

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Glycolysis: Energy Investment

2

1 3

4

5

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Glycolysis: Energy Production

In reactions 6-10 of glycolysis, energy is generated as

• sugar phosphates are cleaved to triose phosphates.

• four ATP molecules are produced.

37

Glycolysis: Reactions 6-10

6

7

8

9

10

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In glycolysis, • two ATP add phosphate to glucose and fructose-6-

phosphate.

• four ATP form as phosphate groups add to ADP.

• there is a net gain of 2 ATP and 2 NADH. C6H12O6 + 2ADP + 2Pi + 2NAD+ Glucose 2 C3H3O3

– + 2ATP + 2NADH + 4H+ Pyruvate

Glycolysis: Overall Reaction

39

Learning Check

In glycolysis, what compounds provide phosphate groups for the production of ATP?

40

Solution

In glycolysis, what compounds provide phosphate groups for the production of ATP?

In reaction 7, phosphate groups from two 1,3-

bisphosphoglycerate molecules are transferred to ADP to form two ATP.

In reaction 10, phosphate groups from two phosphoenolpyruvate molecules are used to form two more ATP.

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Under aerobic conditions (oxygen present), • three-carbon pyruvate is decarboxylated. • two-carbon acetyl CoA and CO2 are produced. O O Pyruvate || || dehydrogenase CH3—C—C—O– + HS—CoA + NAD+ Pyruvate O || CH3—C—S—CoA + CO2 + NADH Acetyl CoA

Pyruvate: Aerobic Conditions

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Under anaerobic conditions (without oxygen), • pyruvate is reduced to lactate. • NADH oxidizes to NAD+, allowing glycolysis to

continue. O O Lactate || || dehydrogenase CH3—C—C—O–+ NADH + H+

Pyruvate

OH O | || CH3—CH—C—O– + NAD+ Lactate

Pyruvate: Anaerobic Conditions

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During strenuous exercise, • anaerobic conditions are produced in muscles. • oxygen is depleted. • lactate accumulates. OH │ C6H12O6 + 1ADP + 2Pi 2CH3–CH –COO– + 2ATP Glucose Lactate • muscles tire and become painful. After exercise, a person breathes heavily to repay the oxygen debt and reform pyruvate in the liver.

Lactate in Muscles

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Pathways for Pyruvate

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Match the following terms with the descriptions. 1) catabolic reactions 2) coenzymes 3) glycolysis 4) lactate A. produced during anaerobic conditions B. reaction series that converts glucose to pyruvate C. metabolic reactions that break down large molecules to

smaller molecules + energy D. substances that remove or add H atoms in oxidation and

reduction reactions

Learning Check

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Match the following terms with the descriptions. 1) catabolic reactions 2) coenzymes 3) glycolysis 4) lactate A. 4 produced during anaerobic conditions B. 3 reaction series that converts glucose to pyruvate C. 1 metabolic reactions that break down large molecules

to smaller molecules + energy D. 2 substances that remove or add H atoms in oxidation

and reduction reactions

Solution

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18.5 The Citric Acid Cycle

Chapter 18 Metabolic Pathways and Energy Production

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In Stage 3, the citric acid cycle • operates under aerobic conditions only.

• oxidizes the two-carbon acetyl group in acetyl CoA to 2CO2.

• produces reduced coenzymes NADH and FADH2, and one ATP directly.

Citric Acid Cycle

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Citric Acid Cycle Overview

In the citric acid cycle, • acetyl (2-carbon)

bonds to oxaloacetate (4-carbon) to form citrate (6-carbon).

• oxidation and decarboxylation reactions convert citrate to oxaloacetate.

• oxaloacetate bonds with another acetyl to repeat the cycle.

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Citric Acid Cycle

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Reaction 1: Formation of Citrate

Oxaloacetate combines with the two-carbon acetyl group to form citrate.

Oxaloacetate Acetyl CoA Citrate

O

C O O –

C H 2

C

C O O –

S C o A

O C C H 3

C O O –

C H 2

C O O –

H O C C H 2

C O O –

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Reaction 2: Isomerization to Isocitrate

Citrate • isomerizes to isocitrate. • converts the tertiary –OH group in citrate to a

secondary –OH in isocitrate that can be oxidized.

Citrate Isocitrate

C O O –

C H 2

C O O –

H O C C H 2

C O O –

H H O H

C O O –

C

C O O –

C C H 2

C O O –

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Summary of Reactions 1 and 2

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Reaction 3: Oxidative Decarboxylation (1)

Isocitrate undergoes decarboxylation (carbon removed as CO2). • The –OH oxidizes to a ketone releasing H+ and 2 e–. • Coenzyme NAD+ is reduced to NADH.

α-Ketoglutarate Isocitrate

+ N A D H + C O 2 O

H

C O O –

C

H C

C H 2

C O O –

H H O

H

C O O –

C

C O O –

C

C H 2

C O O –

NAD+

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Reaction 4: Oxidative Decarboxylation (2)

α-Ketoglutarate • undergoes decarboxylation to form succinyl CoA. • produces a 4-carbon compound that bonds to CoA. • provides H+ and 2 e– to form NADH.

α-Ketoglutarate Succinyl CoA

NAD+

C o A

O S C C H 2

C H 2

C O O –

+ N A D H + C O 2

O

C O O –

C C H 2

C H 2

C O O –

CoA-SH

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Summary Reactions 3 and 4

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Reaction 5: Hydrolysis

Succinyl CoA undergoes hydrolysis, adding a phosphate to GDP to form GTP, a high-energy compound.

CoAS

O

COO-

C

CH2

CH2

COO-

COO-

CH2

CH2 CoA+ GDP + Pi + GTP +

Succinyl CoA Succinate

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Succinate undergoes dehydrogenation • by losing 2 H and forming a double bond. • providing 2 H to reduce FAD to FADH2.

Reaction 6: Dehydrogenation

+ FAD + FADH2

C O O –

C O O –

C H 2

C H 2 H

H

C O O –

C O O –

C

C

F u m a r a t e S u c c i n a t e

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Summary of Reactions 5 and 6

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Reaction 7: Hydration of Fumarate

Fumarate forms malate when water is added to the double bond.

+ H 2 O H H

C O O –

C H H O C

C O O –

m a l a t e f u m a r a t e

H

H

C O O –

C O O –

C

C

Fumarate Malate

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Reaction 8: Dehydrogenation

Malate undergoes dehydrogenation • to form oxaloacetate with a C=O double bond. • providing 2 H for reduction of NAD+ to NADH + H+.

+ NAD+

C O O –

C O O –

O

C H 2

C N A D H

o x a l o a c e t a t e

+ H +

m a l a t e

H H

C O O –

C

H H O C

C O O –

Malate Oxaloacetate

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Summary of Reactions 7 and 8

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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.

Summary of the Citric Acid Cycle

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Acetyl CoA + 3NAD+ + FAD + GDP + Pi + 2H2O 2CO2 + 3NADH + 2H+ + FADH2 + CoA + GTP

Overall Chemical Reaction for the Citric Acid Cycle

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How many of each are produced in one turn of the citric acid cycle? A ___ CO2

B. ___ NADH C. ___ FADH2 D. ___ GTP

Learning Check

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How many of each are produced in one turn of the citric acid cycle? A 2 CO2

B. 3 NADH C. 1 FADH2 D. 1 GTP

Solution

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18.6 Electron Transport

Chapter 18 Metabolic Pathways and Energy Production

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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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Electron Transport

Electron transport • uses electron carriers.

• transfers hydrogen ions and electrons from NADH and FADH2 until they combine with oxygen.

• forms H2O.

• produces ATP energy.

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Electron Carriers

Electron carriers • are oxidized and reduced as hydrogen and/or electrons

are transferred from one carrier to the next. • are FMN, Fe-S, Coenzyme Q, and cytochromes. e l e c t r o n c a r r i e r A H 2 ( r e d u c e d )

e l e c t r o n c a r r i e r B H 2 ( r e d u c e d )

e l e c t r o n c a r r i e r B ( o x i d i z e d )

e l e c t r o n c a r r i e r A ( o x i d i z e d )

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Iron-Sulfur (Fe-S) Clusters

Fe-S clusters • are groups of proteins containing iron ions and sulfide. • accept electrons to reduce Fe3+ to Fe2+, and lose

electrons to re-oxidize Fe2+ to Fe3+.

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FMN (Flavin Mononucleotide)

FMN coenzyme • contains flavin,

ribitol, and a phosphate.

• accepts 2H+ + 2 e– to form reduced coenzyme FMNH2.

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Coenzyme Q (Q or CoQ)

Coenzyme Q (Q or CoQ) is • a mobile electron carrier derived from quinone. • reduced when the keto groups accept 2H+ and 2 e–.

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Cytochromes

Cytochromes (cyt) are • proteins containing

heme groups with iron ions.

Fe3+ + 1 e– Fe2+

• abbreviated as: cyt a, cyt a3, cyt b,

cyt c, and cyt c1.

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Learning Check

Write the abbreviation for each. A. reduced form of coenzyme Q B. oxidized form of flavin mononucleotide C. reduced form of iron in cytochrome c

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Solution

Write the abbreviation for each. A. reduced form of coenzyme Q CoQH2, or QH2 B. oxidized form of flavin mononucleotide FMN C. reduced form of cytochrome c Cyt c (Fe2+)

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Learning Check

Indicate whether the electron carrier in each is oxidized or reduced.

A. FMNH2 FMN

B. Cyt b (Fe3+) Cyt b (Fe2+)

C. Q QH2

D. Cyt c (Fe2+) Cyt c (Fe3+)

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Solution

Indicate whether the electron carrier in each is oxidized or reduced.

A. FMNH2 FMN oxidized

B. Cyt b (Fe3+) Cyt b (Fe2+) reduced

C. Q QH2 reduced

D. Cyt c (Fe2+) Cyt c (Fe3+) oxidized

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In the electron transport system, the electron carriers are • attached to the inner membrane of the mitochondrion. • organized into four protein complexes. Complex I NADH dehydrogenase Complex II Succinate dehydrogenase Complex III CoQ-Cytochrome c reductase Complex IV Cytochrome c oxidase

Electron Transport System

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Electron Transport Chain

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At Complex I, • hydrogen and electrons are transferred from NADH to

FMN. NADH + H+ + FMN NAD+ + FMNH2

• FMNH2 transfers hydrogen to Fe-S clusters and then to

coenzyme Q, reducing Q and regenerating FMN. FMNH2 + Q QH2 + FMN

• QH2, a mobile carrier, transfers hydrogen to Complex III.

Complex I: NADH Dehydrogenase

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At Complex II, with a lower energy level than Complex I, • FADH2 transfers hydrogen and electrons to coenzyme

Q, reducing Q and regenerating FAD. FADH2 + Q QH2 + FAD

• QH2, a mobile carrier, transfers hydrogen to Complex III.

Complex II: Succinate Dehydrogenase

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At Complex III, electrons are transferred • from QH2 to two Cyt b, which reduces Cyt b and

regenerates Q. 2Cyt b (Fe3+) + QH2 2Cyt b (Fe2+) + Q + 2H+

• from Cyt b to Fe-S clusters and to Cyt c, the second

mobile carrier. 2Cyt c (Fe3+) + 2Cyt b (Fe2+) 2Cyt c (Fe2+) + 2Cyt b (Fe3+)

Complex III: CoQ-Cytochrome c reductase

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Complex IV: Cytochrome c Oxidase

• At Complex IV, electrons are transferred from • Cyt c to Cyt a.. 2Cyt a (Fe3+) + 2Cyt c (Fe2+) 2Cyt a (Fe2+) + 2Cyt c (Fe3+)

• Cyt a to Cyt a3, which provides the electrons to

combine H+ and oxygen to form water. 4H+ + O2 + 4 e- (from Cyt a3) 2H2O

Complex IV

85

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Learning Check

Match each with their function. 1) FMN 2) Q 3) Cyt c A. accepts H and electrons from NADH + H+ B. a mobile carrier between Complex II and III C. carries electrons from Complex I and II to Complex III D. accepts H and electrons from FADH2

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Solution

Match each with their function. 1) FMN 2) Q 3) Cyt c A. 1 accepts H and electrons from NADH + H+ B. 3 a mobile carrier between Complex II and III C. 2 carries electrons from Complex I and II to Complex III D. 2 accepts H and electrons from FADH2

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Classify each as a product of the 1) citric acid cycle or 2) electron transport chain. A. CO2 B. FADH2 C. NAD+ D. NADH E. H2O

Learning Check

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Classify each as a product of the 1) citric acid cycle or 2) electron transport chain. A. 1 CO2 B. 1 FADH2 C. 2 NAD+ D. 1 NADH E. 2 H2O

Solution

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Chapter 18 Metabolic Pathways and Energy Production

18.7 Oxidation Phosphorylation and ATP

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Chemiosmotic Model

In the chemiosmotic model • protons (H+) from Complexes I, III, and IV move

into the intermembrane space. • a proton gradient is created. • protons return to matrix through ATP synthase, a

protein complex. • the flow of protons provides energy for ATP

synthesis (oxidative phosphorylation). ADP + Pi + Energy ATP

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ATP Synthase

At ATP synthase, • protons flow back to

the matrix through a channel in the protein complex.

• energy is generated to drive ATP synthesis.

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Chemiosmotic Model of Electron Transport

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In electron transport, sufficient energy is provided from • NADH (Complex I) oxidation for 3 ATPs. NADH + 3 ADP + 3Pi NAD+ + 3 ATP

• FADH2 (Complex II) oxidation for 2 ATPs. FADH2 + 2 ADP + 2Pi FAD + 2 ATP

Electron Transport and ATP

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ATP from Electron Transport

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ATP Energy from Glucose

The complete oxidation of glucose yields • 6CO2, • 6H2O, and • 36 ATP.

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In glycolysis • glucose forms 2 pyruvate, 2 ATP, and 2 NADH. • NADH produced in the cytoplasm cannot enter the

mitochondria. • a shuttle compound (glycerol-3-phosphate) moves

hydrogen and electrons into the mitochondria to FAD, which forms FADH2.

• each FADH2 provides 2 ATP. Glucose 2 pyruvate + 6 ATP

ATP from Glycolysis

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ATP from Glycolysis

Reaction Pathway ATP for One Glucose ATP from Glycolysis Activation of glucose -2 ATP Oxidation of 2 NADH (as FADH2) 4 ATP Direct ADP phosphorylation (two triose) 4 ATP 6 ATP Summary: C6H12O6 2 pyruvate + 2H2O + 6 ATP glucose

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ATP from Two Pyruvate

Under aerobic conditions • 2 pyruvate are oxidized to 2 acetyl CoA and 2 NADH. • 2 NADH enter electron transport to provide 6 ATP. Summary: 2 Pyruvate 2 Acetyl CoA + 6 ATP

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• One turn of the citric acid cycle provides 3 NADH x 3 ATP = 9 ATP 1 FADH2 x 2 ATP = 2 ATP 1 GTP x 1 ATP = 1 ATP Total = 12 ATP Acetyl CoA 2CO2 + 12 ATP • Because each glucose provides two acetyl CoA, two

turns of the citric acid cycle produce 24 ATP. 2 Acetyl CoA 4CO2 + 24 ATP

ATP from Citric Acid Cycle

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ATP from Citric Acid Cycle

Reaction Pathway ATP for One Glucose ATP from Citric Acid Cycle Oxidation of 2 isocitrate (2 NADH) 6 ATP Oxidation of 2 α-ketoglutarate (2 NADH) 6 ATP 2 direct substrate phosphorylations (2 GTP) 2 ATP Oxidation of 2 succinate (2 FADH2) 4 ATP Oxidation of 2 malate (2 NADH) 6 ATP

Total 24 ATP Summary: 2 Acetyl CoA 4CO2 + 2H2O + 24 ATP

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One glucose molecule undergoing complete oxidation provides: From glycolysis 6 ATP From 2 Pyruvate 6 ATP From 2 Acetyl CoA 24 ATP Overall ATP Production for One Glucose: C6H12O6 + 6O2 + 36 ADP + 36Pi Glucose 6CO2 + 6H2O + 36 ATP

Total ATP from Glucose

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Learning Check

Indicate the ATP yield for each under aerobic conditions. A. Complete oxidation of glucose B. FADH2 C. Acetyl CoA in citric acid cycle D. NADH E. Pyruvate decarboxylation

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Solution

Indicate the ATP yield for each under aerobic conditions. A. Complete oxidation of glucose 36 ATP B. FADH2 2 ATP C. Acetyl CoA in citric acid cycle 12 ATP D. NADH 3 ATP E. Pyruvate decarboxylation 3 ATP

105

Chapter 18 Metabolic Pathways and Energy Production

18.8 Oxidation of Fatty Acids

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106

β-Oxidation of Fatty Acids

In reaction 1, oxidation • removes H atoms from

the α and β carbons. • forms a trans C=C bond. • reduces FAD to FADH2.

β α

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β-Oxidation of Fatty Acids

In reaction 2, hydration • adds water across the

trans C=C bond. • forms a hydroxyl group

(—OH) on the β carbon.

β α

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β-Oxidation of Fatty Acids

In reaction 3, a second oxidation • oxidizes the hydroxyl

group. • forms a keto group on

the β carbon. • reduces NAD+ to

NADH.

β α

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β-Oxidation of Fatty Acids

In reaction 4, fatty acyl CoA is split • between the α and β

carbons. • to form acetyl CoA

and a shortened fatty acyl CoA that repeats Steps 1-4 of β-oxidation.

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110

Learning Check

Match the reactions of β-oxidation with each. 1) oxidation 1 2) hydration 3) oxidation 2 4) fatty acyl CoA cleaved A. Water is added. B. FADH2 forms. C. A two-carbon unit is removed. D. A hydroxyl group is oxidized. E. NADH forms.

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Solution

Match the reactions of β-oxidation with each: 1) oxidation 1 2) hydration 3) oxidation 2 4) fatty acyl CoA cleaved A. 2 Water is added. B. 1 FADH2 forms. C. 4 A two-carbon unit is removed. D. 3 A hydroxyl group is oxidized. E. 3 NADH forms.

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Cycles of β-Oxidation

The number of β-oxidation cycles • depends on the length of a fatty acid. • is one less than the number of acetyl CoA groups

formed. Carbons in Acetyl CoA β-Oxidation Cycles Fatty Acid (C/2) (C/2 –1) 12 6 5 14 7 6 16 8 7 18 9 8

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β-Oxidation of Myristic (C14) Acid

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β-Oxidation of Myristic (C14) Acid (continued)

7 Acetyl CoA

6 cycles

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Learning Check

A. The number of acetyl CoA groups produced by the complete β-oxidation of palmitic acid (C16) is

1) 16. 2) 8. 3) 7. B. The number of oxidation cycles to completely

oxidize palmitic acid (C16 ) is 1) 16. 2) 8. 3) 7.

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Solution

A. The number of acetyl CoA groups produced by the complete β-oxidation of palmitic acid (C16 ) is

2) 8. B. The number of oxidation cycles to completely oxidize

palmitic acid (C16) is 3) 7.

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β-Oxidation and ATP

• Activation of a fatty acid requires 2 ATP • One cycle of oxidation of a fatty acid produces 1 NADH 3 ATP 1 FADH2 2 ATP • Acetyl CoA entering the citric acid cycle produces 1 Acetyl CoA 12 ATP

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ATP for Lauric Acid C12

ATP production for lauric acid (12 carbons): Activation of lauric acid -2 ATP 6 acetyl CoA 6 acetyl CoA x 12 ATP/acetyl CoA 72 ATP 5 oxidation cycles 5 NADH x 3 ATP/NADH 15 ATP 5 FADH2 x 2 ATP/FADH2 10 ATP Total 95 ATP

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Learning Check

The total ATP produced from the β-oxidation of stearic acid (C18) is.

1) 108 ATP. 2) 146 ATP. 3) 148 ATP.

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Solution

The total ATP produced from the β-oxidation of stearic acid (C18) is:

2) 146 ATP Activation -2 ATP 9 Acetyl CoA x 12 ATP 108 ATP 8 NADH x 3 ATP 24 ATP 8 FADH2 x 2 ATP 16 ATP 146 ATP

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Ketone Bodies

If carbohydrates are not available, • body fat breaks

down to meet energy needs.

• compounds called ketone bodies form.

Ketone bodies

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Formation of Ketone Bodies

Ketone bodies form • if large amounts of acetyl CoA accumulate. • when two acetyl CoA molecules form acetoacetyl CoA. • when acetoacetyl CoA hydrolyzes to acetoacetate. • when acetoacetate reduces to β-hydroxybutyrate or

loses CO2 to form acetone, both ketone bodies.

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Ketosis

Ketosis occurs • in diabetes, diets high in

fat, and starvation.

• as ketone bodies accumulate.

• when acidic ketone bodies lower blood pH below 7.4 (acidosis).

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Ketone Bodies and Diabetes

In diabetes • insulin does not

function properly. • glucose levels are

insufficient for energy needs.

• fats are broken down to acetyl CoA.

• ketone bodies form.

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Chapter 18 Metabolic Pathways and Energy Production

18.9 Degradation of Amino Acids

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126

Proteins in the Body

Proteins provide • amino acids for

protein synthesis. • nitrogen atoms for

nitrogen-containing compounds.

• energy when carbohydrate and lipid resources are not available.

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Transamination

In transamination • amino acids are degraded in the liver. • an amino group is transferred from an amino acid to

an α-keto acid, usually α-ketoglutarate. • a new amino acid, usually glutamate, is formed. • a new α-keto acid is formed.

128

A Transamination Reaction

NH3

+ O | || CH3—CH—COO– + –OOC—C—CH2—CH2—COO–

Alanine α-Ketoglutarate

O NH3

+ || | CH3—C—COO– + –OOC—CH—CH2—CH2—COO–

Pyruvate Glutamate (new α-ketoacid) (new amino acid)

Alanine transaminase

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Synthesis of Amino Acids

In humans, transamination of compounds from glycolysis or the citric acid cycle produces nonessential amino acids.

Copyright © 2009 by Pearson Education, Inc.

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Oxidative Deamination

Oxidative deamination • removes the amino group as an ammonium ion from

glutamate. • provides α-ketoglutarate for transamination. NH3

+ Glutamate │ dehydrogenase –OOC—CH—CH2—CH2—COO– + NAD+ + H2O Glutamate

O || –OOC—C—CH2—CH2—COO– + NH4

+ + NADH α-Ketoglutarate

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Learning Check

Write the structures and names of the products for the transamination of α-ketoglutarate by aspartate. NH3

+ | –OOC—CH—CH2—COO– aspartate O || –OOC—C—CH2—CH2—COO–

α-ketoglutarate

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Solution

Write the structures and names of the products for the transamination of α-ketoglutarate by aspartate. O || –OOC—C—CH2—COO– Oxaloacetate NH3

+ | –OOC—CH—CH2—CH2—COO–

Glutamate

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Urea Cycle

The urea cycle • removes toxic ammonium ions from amino acid

degradation. • converts ammonium ions to urea in the liver. O + || 2NH4 + CO2 H2N—C—NH2 Ammonium ion Urea • produces 25-30 g of urea daily for urine formation

in the kidneys.

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Carbon Atoms from Amino Acids

Carbon skeletons of amino acids • form intermediates of the citric acid cycle. • produce energy.

Three-carbon skeletons: alanine, serine, and cysteine pyruvate Four-carbon skeletons: aspartate, asparagine oxaloacetate Five-carbon skeletons: glutamine, glutamate, proline, arginine, histidine glutamate

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Intermediates of the Citric Acid Cycle from Amino Acids

136

Learning Check

Match each the intermediate with the amino acid that provides its carbon skeleton. 1) pyruvate 2) fumarate 3) α-ketoglutarate A. cysteine B. glutamine C. aspartate D. serine

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Solution

Match each the intermediate with the amino acid that provides its carbon skeleton. 1) pyruvate 2) fumarate 3) α-ketoglutarate A. 1 cysteine B. 3 glutamine C. 2 aspartate D. 1 serine

138

Overview of Metabolism

In metabolism • catabolic pathways degrade large molecules. • anabolic pathway synthesize molecules. • branch points determine which compounds are

degraded to acetyl CoA to meet energy needs or converted to glycogen for storage.

• excess glucose is converted to body fat. • fatty acids and amino acids are used for energy when

carbohydrates are not available. • some amino acids are produced by transamination.

139

Overview of Metabolism

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