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7 Focus on Health & Medicine: Hydrogen Cyanide

7 Focus on Health & Medicine: Hydrogen Cyanide

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740



DIGESTION AND THE CONVERSION OF FOOD INTO ENERGY



CHAPTER HIGHLIGHTS

KEY TERMS

Acetyl CoA (23.4)

Adenosine 5'-diphosphate (ADP, 23.3)

Adenosine 5'-triphosphate (ATP, 23.3)

Anabolism (23.1)

Catabolism (23.1)

Citric acid cycle (23.5)



Coenzyme A (23.4)

Coupled reactions (23.3)

Electron transport chain (23.6)

Flavin adenine dinucleotide (FAD, 23.4)

Metabolism (23.1)

Mitochondrion (23.1)



Nicotinamide adenine dinucleotide

(NAD+, 23.4)

Oxidative phosphorylation (23.6)

Phosphorylation (23.3)



KEY CONCEPTS

❶ What is metabolism and where is energy produced in

cells? (23.1)

• Metabolism is the sum of all of the chemical reactions that

take place in an organism. Catabolic reactions break down

large molecules and release energy, while anabolic reactions

synthesize larger molecules and require energy.

• Energy is produced in the mitochondria, sausage-shaped

organelles that contain an outer and inner cell membrane.

Energy is produced in the matrix, the area surrounded by

the inner membrane.

❷ What are the four stages of metabolism? (23.2)

• Metabolism begins with digestion in stage [1], in

which large molecules—polysaccharides, proteins, and

triacylglycerols—are hydrolyzed to smaller molecules—

monosaccharides, amino acids, fatty acids, and glycerol.

• In stage [2], biomolecules are degraded into two-carbon

acetyl units.

• The citric acid cycle comprises stage [3]. The citric acid

cycle converts two carbon atoms to two molecules of CO2,

and forms reduced coenzymes, NADH and FADH2, which

carry electrons and energy to the electron transport chain.

• In stage [4], the electron transport chain and oxidative

phosphorylation produce ATP, and oxygen is converted to

water.

❸ What is ATP and how do coupled reactions with ATP drive

energetically unfavorable reactions? (23.3)

• ATP is the primary energy-carrying molecule in metabolic

pathways. The hydrolysis of ATP cleaves one phosphate

group and releases 7.3 kcal/mol of energy.

• The hydrolysis of ATP provides the energy to drive a

reaction that requires energy. A pair of reactions of this sort

is said to be coupled.

❹ List the main coenzymes in metabolism and describe their

roles. (23.4)

• Nicotinamide adenine dinucleotide (NAD+) is a biological

oxidizing agent that accepts electrons and protons, thus

generating its reduced form NADH. NADH is a reducing

agent that donates electrons and protons, re-forming NAD+.

• Flavin adenine dinucleotide (FAD) is a biological oxidizing

agent that accepts electrons and protons, thus yielding its



smi26573_ch23.indd 740



reduced form, FADH2. FADH2 is a reducing agent that

donates electrons and protons, re-forming FAD.

• Coenzyme A reacts with acetyl groups (CH3CO–) to form

high-energy thioesters that deliver two-carbon acetyl groups

to other substrates.

❺ What are the main features of the citric acid cycle? (23.5)

• The citric acid cycle is an eight-step cyclic pathway that

begins with the addition of acetyl CoA to a four-carbon

substrate. In the citric acid cycle, two carbons are converted

to CO2 and four molecules of reduced coenzymes are

formed. One molecule of a high-energy nucleoside

triphosphate is also formed.

❻ What are the main components of the electron transport

chain and oxidative phosphorylation? (23.6)

• The electron transport chain is a multistep process that

takes place in the inner membrane of mitochondria.

Electrons from reduced coenzymes enter the chain and are

passed from one molecule to another in a series of redox

reactions, releasing energy along the way. At the end of the

chain, electrons and protons react with inhaled oxygen to

form water.

• H+ ions are pumped across the inner membrane of the

mitochondrion, forming a high concentration of H+ ions in

the intermembrane space, thus creating a potential energy

gradient. When the H+ ions travel through the channel in the

ATP synthase enzyme, this energy is used to convert ADP

to ATP—a process called oxidative phosphorylation.

❼ Why do compounds such as cyanide act as poisons when

they disrupt the electron transport chain? (23.7)

• Since all catabolic pathways converge at the electron

transport chain, these steps are needed to produce energy

for normal cellular processes. Compounds that disrupt

a single step can halt ATP synthesis so that an organism

cannot survive.

• Cyanide from HCN irreversibly binds to the Fe3+ ion of the

enzyme cytochrome oxidase and, as a result, Fe3+ cannot be

reduced to Fe2+ and water cannot be formed from oxygen.

Since the electron transport chain is disrupted, energy is

not generated for oxidative phosphorylation, ATP is not

synthesized, and cell death often follows.



12/19/08 2:28:15 PM



PROBLEMS



741



PROBLEMS

Selected in-chapter and end-of-chapter problems have brief answers provided in Appendix B.



Metabolism

23.15

23.16

23.17

23.18

23.19



23.20

23.21



23.22



23.27



What is the difference between catabolism and

anabolism?

What is the difference between metabolism and

digestion?

Describe the main features of a mitochondrion. Where

does energy production occur in a mitochondrion?

Explain why mitochondria are called the powerhouses of

the cell.

Place the following steps in the catabolism of carbohydrates

in order: the electron transport chain, the conversion of

glucose to acetyl CoA, the hydrolysis of starch, oxidative

phosphorylation, and the citric acid cycle.

Describe the main features of the four stages of

catabolism.

In what stage of catabolism does each of the following

processes occur?

a. cleavage of a protein with chymotrypsin

b. oxidation of a fatty acid to acetyl CoA

c. oxidation of malate to oxaloacetate with NAD+

d. conversion of ADP to ATP with ATP synthase

e. hydrolysis of starch to glucose with amylase

In what stage of catabolism does each of the following

processes occur?

a. conversion of a monosaccharide to acetyl CoA

b. hydrolysis of a triacylglycerol with lipase

c. reaction of oxygen with protons and electrons to

form water

d. conversion of succinate to fumarate with FAD

e. degradation of a fatty acid to acetyl CoA



ATP and Coupled Reactions

23.23

23.24

23.25



O

CH3



C



O

O



P



O−



O−

acetyl phosphate



23.26



smi26573_ch23.indd 741



Energy change

succinate + HSCoA

ATP + H2O



23.28



succinyl CoA + H2O

2–



ADP + HPO4



+9.4 kcal/mol

–7.3 kcal/mol



a. Combine the equations and write the coupled reaction.

b. Is the coupled reaction energetically favorable?

Explain.

The hydrolysis of succinyl CoA to succinate and

coenzyme A releases energy, and the phosphorylation of

ADP requires energy as shown in the given equations.

Energy change



succinyl CoA + H2O

ADP + HPO42–



23.29



23.30



23.31



What are coupled reactions and why does coupling

occur?

Explain why ATP and GTP are called “high-energy”

compounds.

Acetyl phosphate is another example of a high-energy

phosphate. What products would be formed when acetyl

phosphate is hydrolyzed with water?



The reaction of succinate with coenzyme A to form

succinyl CoA requires energy, and the hydrolysis of ATP

releases energy as shown in the given equations.



succinate + HSCoA



–9.4 kcal/mol



ATP + H2O



+7.3 kcal/mol



a. Combine the equations and write the coupled reaction.

b. Is the coupled reaction energetically favorable?

Explain.

The phosphorylation of glucose with HPO42– forms

glucose 1-phosphate and water and requires 5.0 kcal/mol

of energy.

a. Write the equation for this reaction.

b. This unfavorable reaction can be driven by the

hydrolysis of ATP to ADP. Write an equation for the

coupled reaction.

c. Calculate the energy change for the coupled reaction.

Write an equation for the reverse reaction described

in Problem 23.29—that is, the hydrolysis of glucose

1-phosphate to form glucose and HPO42–. What is the

energy change in this reaction?

The phosphorylation of fructose 6-phosphate to form

fructose 1,6-bisphosphate and water requires 3.9 kcal/mol

of energy.

fructose 6-phosphate + HPO42–

fructose 1,6-bisphosphate + H2O



a. What is the energy change for the reverse reaction—

that is, the hydrolysis of fructose 1,6-bisphosphate to

form fructose 6-phosphate?

b. Write a coupled reaction that shows how the energy

from ATP hydrolysis (–7.3 kcal/mol) can be used to

drive the given reaction.

c. What is the energy change for the coupled reaction?



ADP undergoes hydrolysis in a similar manner to ATP;

that is, a P O bond is cleaved. Draw the structure of the

product of ADP hydrolysis.



12/19/08 2:28:15 PM



742



23.32



DIGESTION AND THE CONVERSION OF FOOD INTO ENERGY



a. Use the values in Problem 23.31 to calculate the

energy change in the following reaction.



fructose 1,6-bisphosphate + ADP



23.33



a.



fructose 6-phosphate + ATP



b. Is this reaction energetically favorable or unfavorable?

c. Write this reaction using curved arrow symbolism.

d. Can this reaction be used to synthesize ATP from

ADP? Explain.

Refer to the following equations to answer the questions.



–11.8 kcal/mol



ADP + HPO42–



–7.3 kcal/mol



23.34



23.35



23.36



a. Write the equation for the coupled reaction

of 1,3-bisphosphoglycerate with ADP to form

3-phosphoglycerate and ATP.

b. Calculate the energy change for this coupled reaction.

c. Can this reaction be used to synthesize ATP from

ADP? Explain.

Refer to the equations in Problem 23.33 to answer the

following questions.

a. Write the equation for the coupled reaction

of 3-phosphoglycerate with ATP to form

1,3-bisphosphoglycerate and ADP.

b. Calculate the energy change for this coupled reaction.

c. Is this reaction energetically favorable? Explain.

(a) Draw the structure of the high-energy nucleoside

triphosphate GTP. (b) Draw the structure of the

hydrolysis product formed when one phosphate is

removed.

If the phosphorylation of GDP to form GTP requires

7.3 kcal/mol of energy, how much energy is released

when GTP is hydrolyzed to GDP?



Coenzymes

23.37

23.38

23.39



23.40



23.41



Classify each substance as an oxidizing agent, a reducing

agent, or neither: (a) FADH2; (b) ATP; (c) NAD+.

Classify each substance as an oxidizing agent, a reducing

agent, or neither: (a) NADH; (b) ADP; (c) FAD.

When a substrate is oxidized, is NAD+ oxidized or

reduced? Is NAD+ an oxidizing agent or a reducing

agent?

When a substrate is reduced, is FADH2 oxidized or

reduced? Is FADH2 an oxidizing agent or a reducing

agent?

Label each reaction as an oxidation or a reduction and

give the coenzyme, NAD+ or NADH, which might be

used to carry out the reaction. Write each reaction using

curved arrow symbolism.



smi26573_ch23.indd 742



CH2OH



b.

23.42



Label each reaction as an oxidation or a reduction and

give the coenzyme, NAD+ or NADH, which might be

used to carry out the reaction. Write each reaction using

curved arrow symbolism.

a. CH3CH2CHO

CH3CH2CH2OH



1,3-bisphosphoglycerate + H2O

3-phosphoglycerate + HPO42–



O



CHO



Energy change



ATP + H2O



OH



CH2OH



CHO



OCH3



OCH3



b.



Citric Acid Cycle

23.43



What reactions in the citric acid cycle have each of the

following characteristics?

a. The reaction generates NADH.

b. CO2 is removed.

c. The reaction utilizes FAD.

d. The reaction forms a new carbon–carbon single bond.

What reactions in the citric acid cycle have each of the

following characteristics?

a. The reaction generates FADH2.

b. The organic substrate is oxidized.

c. The reaction utilizes NAD+.

d. The reaction breaks a carbon–carbon bond.

(a) Which intermediate(s) in the citric acid cycle contain

two chirality centers? (b) Which intermediate(s) contain a

2° alcohol?

(a) Which intermediate(s) in the citric acid cycle contain

one chirality center? (b) Which intermediate(s) contain a

3° alcohol?

The conversion of isocitrate to α-ketoglutarate in step

[3] of the citric acid cycle actually occurs by a two-step

process: isocitrate is converted first to oxalosuccinate,

which then goes on to form α-ketoglutarate.



23.44



23.45



23.46



23.47



CO2−



CO2−



CH2





H



C



CO2



HO



C



H





CO2



isocitrate



[3a]



CO2−



CH2

H







[3b]



CH2



C



CO2



C



O



C







CO2−



CO2



oxalosuccinate



CH2

O



α-ketoglutarate



a. Classify reaction [3a] as an oxidation, reduction, or

decarboxylation.

b. Classify reaction [3b] as an oxidation, reduction, or

decarboxylation.

c. For which step is NAD+ necessary?

d. Why is the enzyme that catalyzes this reaction called

isocitrate dehydrogenase?



12/19/08 2:28:16 PM



PROBLEMS



23.48



743



The conversion of citrate to isocitrate in step [2] of the

citric acid cycle actually occurs by a two-step process

(steps [2a] and [2b]) with aconitate formed as an

intermediate.









CH2

HO



C







CO2



CH2

CO2



23.49

23.50



CO2



CH2

C







CO2



CH





citrate



[2a]



23.57







CO2



CO2



23.56



[2b]



CH2

H



C



CO2−



HO



C



H







CO2−



aconitate



isocitrate



CO2



a. What atoms are added or removed in each step?

b. Steps [2a] and [2b] are not considered oxidation or

reduction reactions despite the fact that the number

of C H and C O bonds changes in these reactions.

Explain why this is so.

c. From your knowledge of organic chemistry learned in

previous chapters, what type of reaction occurs in step

[2a]? In step [2b]?

In what step does a hydration reaction occur in the citric

acid cycle?

What products of the citric acid cycle are funneled into

the electron transport chain?



23.58



General Questions and Applications

23.59

23.60

23.61

23.62

23.63



23.64



Electron Transport Chain and

Oxidative Phosphorylation

23.51

23.52



23.53



23.54



23.55



smi26573_ch23.indd 743



Why are the reactions that occur in stage [4] of

catabolism sometimes called aerobic respiration?

What is the role of each of the following in the electron

transport chain: (a) NADH; (b) O2; (c) complexes I–IV;

(d) H+ ion channel?

What is the role of each of the following in the electron

transport chain: (a) FADH2; (b) ADP; (c) ATP synthase;

(d) the inner mitochondrial membrane?

Explain the importance of the movement of H+ ions

across the inner mitochondrial membrane and then

their return passage through the H+ ion channel in ATP

synthase.

What are the final products of the electron transport

chain?



What product is formed from each of the following

compounds during the electron transport chain:

(a) NADH; (b) FADH2; (c) ADP; (d) O2?

Why does one NADH that enters the electron transport

chain ultimately produce 2.5 ATPs, while one FADH2

produces 1.5 ATPs?

How does the energy from the proton gradient result in

ATP synthesis?



23.65

23.66



23.67

23.68

23.69

23.70



How does the metabolism of the two carbons of acetyl

CoA form 10 molecules of ATP?

What is the difference between phosphorylation and

oxidative phosphorylation?

What is the structural difference between ATP and ADP?

What is the structural difference between coenzyme A

and acetyl CoA?

From what you learned about monosaccharides in

Chapter 20 and phosphates in Chapter 23: (a) Draw the

structure of glucose 1-phosphate. (b) Using structures,

write the equation for the hydrolysis of glucose

1-phosphate to glucose and HPO42–.

From what you learned about monosaccharides in

Chapter 20 and phosphates in Chapter 23: (a) Draw the

structure of glucose 6-phosphate. (b) Using structures,

write the equation for the hydrolysis of glucose

6-phosphate to glucose and HPO42–.

How are the citric acid cycle and the electron transport

chain interrelated?

Why is the citric acid cycle considered to be part of the

aerobic catabolic pathways, even though oxygen is not

directly involved in any step in the cycle?

In which tissue would a cell likely have more

mitochondria, the heart or the bone? Explain your choice.

What is the fate of an acetyl CoA molecule after several

turns of the citric acid cycle?

What is the role of stored creatine phosphate in muscles?

Explain how HCN acts as a poison by interfering with the

synthesis of ATP.



12/19/08 2:28:16 PM



24

CHAPTER OUTLINE

24.1



Introduction



24.2



Understanding Biochemical

Reactions



24.3



Glycolysis



24.4



The Fate of Pyruvate



24.5



The ATP Yield from Glucose



24.6



Gluconeogenesis



24.7



The Catabolism of Triacylglycerols



24.8



Ketone Bodies



24.9



Amino Acid Metabolism



CHAPTER GOALS

In this chapter you will learn how to:

❶ Understand the basic features of

biochemical reactions

❷ Describe the main aspects of glycolysis

❸ List the pathways for pyruvate

metabolism

❹ Calculate the energy yield from

glucose metabolism

❺ Describe the main features of

gluconeogenesis

❻ Summarize the process of the

𝛃-oxidation of fatty acids

❼ Calculate the energy yield from fatty

acid oxidation

❽ Identify the structures of ketone

bodies and describe their role in

metabolism

❾ Describe the main components of

amino acid catabolism



A complex set of biochemical pathways converts ingested carbohydrates, lipids, and proteins to

usable materials and energy to meet the body’s needs.



CARBOHYDRATE, LIPID, AND

PROTEIN METABOLISM

THE metabolism of ingested food begins with the hydrolysis of large biomolecules

into small compounds that can be absorbed through the intestinal wall. In Chapter

23 we learned that the last stages of catabolism, which produce energy from acetyl

coenzyme A (acetyl CoA) by means of the citric acid cycle, electron transport

chain, and oxidative phosphorylation, are the same for all types of biomolecules.

The catabolic pathways that form acetyl CoA are different, however, depending on

the particular type of biomolecule. In Chapter 24 we examine the specific metabolic pathways for carbohydrates, lipids, and proteins.



744



smi26573_ch24.indd 744



12/19/08 2:35:19 PM



UNDERSTANDING BIOCHEMICAL REACTIONS



745



24.1 INTRODUCTION

The four stages in metabolism:

Carbohydrates



Proteins



Monosaccharides



Amino acids



Triacylglycerols

[1]

Fatty acids

+

glycerol

[2]



Glycolysis

Fatty acid

oxidation



Amino acid

catabolism

Pyruvate



Recall from Section 23.2 that we can conceptually consider catabolism as the sum of four stages.

Catabolism begins with digestion in stage [1] in which polysaccharides, triacylglycerols, and

proteins are hydrolyzed to smaller compounds that can be absorbed by the bloodstream and delivered to individual cells. Each type of biomolecule is then converted to acetyl CoA by different

pathways in stage [2]. Acetyl CoA enters the citric acid cycle and produces reduced coenzymes,

whose energy is stored in ATP (stages [3] and [4]). Since we already learned many important

facts about stages [1], [3], and [4] of catabolism, we now consider the metabolic pathways that

convert monosaccharides, fatty acids and glycerol, and amino acids to acetyl CoA in stage [2].



Acetyl CoA



• Carbohydrates: Glycolysis converts glucose, the most common monosaccharide, to

pyruvate, which is then metabolized to acetyl CoA (Sections 24.3–24.4).

[3]



Citric acid

cycle



CH2OH

H



Reduced coenzymes



O

H

OH



H



H



OH

[4]



Electron transport

chain and

oxidative phosphorylation



glycolysis



OH

H



2 CH3



O



O



C



C



O

O−



2 CH3



pyruvate



C



SCoA



acetyl CoA



OH



glucose



• Lipids: Fatty acids are converted to thioesters, which are oxidized by a stepwise

procedure that sequentially cleaves two-carbon units from the carbonyl end to form

acetyl CoA (Section 24.7).

O

CH3(CH2)16



C



fatty acid



O

OH



CH3(CH2)16



C



thioester



O

SCoA



9 CH3



C



SCoA



acetyl CoA



• Amino acids: The amino acids formed from protein hydrolysis are often assembled into

new proteins without any other modification. Since excess amino acids are not stored

in the body, they are catabolized for energy as discussed in Section 24.9. The amino

groups (NH2) of amino acids are converted to urea [(NH2)2C O], which is excreted in

urine.



24.2 UNDERSTANDING BIOCHEMICAL REACTIONS

Before examining the specific reactions of glycolysis, let’s pause to consider some principles that

will help us better understand these processes.

The biochemical reactions we learned in Chapter 23 and those we will examine in Chapter 24 are

often challenging for a student to tackle. On the one hand, cells use the basic principles of organic

chemistry in oxidation, reduction, acid–base, and other reactions. On the other hand, the use of

enzymes and coenzymes allows cells to carry out transformations that are not easily replicated

or even possible in the lab, so many reactions take on a new and different appearance. Moreover,

many substrates have several functional groups and these reactions often proceed with complete

selectivity at just one of them.

While it is often difficult to predict the exact product of some reactions, it should be possible to

understand and analyze a reaction by examining the reactants and products, the reagents (coenzymes and other materials), and the enzymes. The name of an enzyme is often a clue as to the

type of reaction. Common types of enzymes encountered in metabolism, such as kinases and

isomerases, are listed in Table 24.1.



smi26573_ch24.indd 745



12/19/08 2:35:24 PM



746



CARBOHYDRATE, LIPID, AND PROTEIN METABOLISM



TABLE 24.1



Common Enzymes in Metabolism



Type of Enzyme



Type of Reaction



Carboxylase



Addition of a carboxylate (–COO–)



Decarboxylase



Removal of carbon dioxide (CO2)



Dehydrogenase



Removal of two hydrogen atoms



Isomerase



Isomerization of one isomer to another



Kinase



Transfer of a phosphate



• A kinase catalyzes the transfer of a phosphate group from one substrate to another.

• An isomerase catalyzes the conversion of one isomer to another.



As an example, consider the conversion of fructose 6-phosphate to fructose 1,6-bisphosphate,

step [3] in glycolysis (Section 24.3). In this reaction, a phosphate group is transferred from ATP

to fructose 6-phosphate.

ATP as a reactant means

“transfer a phosphate.”

C6



O

−O



P



O



CH2



O−



H



CH2OH



O

HO



H



OH

OH



C1



O

ATP



ADP



−O



phosphofructokinase



P



O



CH2



O−



H



fructose 6-phosphate



CH2O



O



P



O−



O−



HO



H



OH

OH



H



O



H



fructose 1,6-bisphosphate

A kinase enzyme means

“transfer a phosphate.”



It would probably be hard for you to predict that this reaction converts only the OH group at C1

to a phosphate, given that the substrate has four OH groups. Nonetheless, it is possible to understand the reaction by looking at all of its components.

• A phosphate is added to fructose 6-phosphate to form fructose 1,6-bisphosphate, a

product with two phosphate groups.

• The new phosphate in the product comes from ATP, a high-energy nucleoside

triphosphate that transfers a phosphate to other compounds—in this case, fructose

6-phosphate.

• Loss of a phosphate from ATP forms ADP.

• The reaction is catalyzed by a kinase enzyme, also indicating that a phosphate is

transferred.



Sample Problems 24.1 and 24.2 illustrate the process in other examples.



smi26573_ch24.indd 746



12/19/08 2:35:26 PM



UNDERSTANDING BIOCHEMICAL REACTIONS



SAMPLE PROBLEM 24.1



747



Analyze the following reaction by considering the functional groups that change and the name

of the enzyme.

O

CH3



C



O

C



O

O







CH3



pyruvate

decarboxylase



pyruvate



C



H



CO2



ANALYSIS



• Consider the functional groups that are added or removed as a clue to the type of reaction.

• Classify the reagent (when one is given) as to the type of reaction it undergoes.

• Use the name of the enzyme as a clue to the reaction type.



SOLUTION



The –COO– of pyruvate is lost as CO2, meaning that a decarboxylation has occurred.

This is supported by the type of enzyme, a decarboxylase, which typically catalyzes

decarboxylations. A carbon–carbon bond is broken in the process, giving CO2 as one of the

products. No coenzyme is used here; the reaction does not involve oxidation, reduction, or

thioester synthesis.



SAMPLE PROBLEM 24.2



Analyze the following reaction by considering the functional groups that change, the coenzyme

utilized, and the name of the enzyme.

O

−O



P



O



CH2



OH



O



CH



C



ADP



O

O



O−



P

O−



O−



ATP



O

−O



phosphoglycerate

kinase



ANALYSIS



SOLUTION



PROBLEM 24.1



O



CH2



O



CH



C



O−



• Consider the functional groups that are added or removed as a clue to the type of reaction.

• Classify the reagent—that is, any coenzyme or other reactant—as to the type of reaction

it undergoes. For example, NAD+ is an oxidizing agent, while NADH is a reducing agent.

ATP transfers phosphate groups to substrates, while ADP accepts phosphate groups from

substrates.

• Use the name of the enzyme as a clue to the reaction type.

A phosphate group is removed from the reactant to give 3-phosphoglycerate. This phosphate

is transferred to the nucleoside diphosphate ADP to form the nucleoside triphosphate ATP.

Since kinase enzymes catalyze the addition or removal of phosphates, the enzyme used for the

reaction is phosphoglycerate kinase. No coenzyme is used here; the reaction does not involve

oxidation, reduction, or thioester synthesis.

Analyze the following reaction by considering the functional groups that change and the name

of the enzyme.

O

−O



P



O



O

O



CH2



C



CH2OH



O−

dihydroxyacetone phosphate



PROBLEM 24.2



P



OH



O−

3-phosphoglycerate



1,3-bisphosphoglycerate



triose phosphate

isomerase



−O



P



O



CH2



OH



O



CH



C



H



O−

glyceraldehyde 3-phosphate



Analyze the following reaction by considering the functional groups that change, the coenzyme

utilized, and the name of the enzyme.

O

−O



P



O



CH2



OH



O



CH



C



O−

glyceraldehyde 3-phosphate



smi26573_ch24.indd 747



+



NAD+

H



NADH + H+



glyceraldehyde 3-phosphate

dehydrogenase



O

−O



P



O



CH2



OH



O



CH



C



O−



O−

3-phosphoglycerate



12/19/08 2:35:26 PM



748



CARBOHYDRATE, LIPID, AND PROTEIN METABOLISM



24.3 GLYCOLYSIS

The metabolism of monosaccharides centers around glucose. Whether it is obtained by the hydrolysis of ingested polysaccharides or stored glycogen (Section 20.6), glucose is the principal monosaccharide used for energy in the human body.

• Glycolysis is a linear, 10-step pathway that converts glucose, a six-carbon

monosaccharide, to two molecules of pyruvate (CH3COCO2–).



The word glycolysis is derived from

the Greek glykys meaning sweet and

lysis meaning splitting.



Glycolysis is an anaerobic pathway that takes place in the cytoplasm and can be conceptually

divided into two parts (Figure 24.1).

• Steps [1]–[5] comprise the energy-investment phase. The addition of two phosphate

groups requires the energy stored in two ATP molecules. Cleavage of a carbon–carbon

bond forms two three-carbon products.

• Steps [6]–[10] comprise the energy-generating phase. Each of the three-carbon products

is ultimately oxidized, forming NADH, and two high-energy phosphate bonds are broken

to form two ATP molecules.



The specific reactions of glycolysis are discussed in Section 24.3A. To better understand these

reactions, recall a few facts from Chapter 23.





FIGURE 24.1



An Overview of Glycolysis

CH2OH

H



O

H

OH



OH



H



HO



H



H

OH

This bond is broken at step [4]. glucose

ATP

1

ADP

2

ATP



3



Energy-investment phase



ADP



4

O

P



O



CH2



C



CH2OH



+



dihydroxyacetone

phosphate

5



P



O



O



CH



C



H



ATP

8

=



P



O



glyceraldehyde

3-phosphate

NAD+

6

NADH + H+

ADP

7



O

−O



CH2



OH



P



Energy-generating phase



9







ADP



10

O

Two molecules of pyruvate are formed

from each molecule of glucose.



CH3



ATP

O



C C O−

pyruvate



In the energy-investment phase of glycolysis, ATP supplies energy needed for steps [1] and [3]. In the energy-generating phase, each

three-carbon product from step [5] forms one NADH and two ATP molecules. Since two glyceraldehyde 3-phosphate molecules are

formed from each glucose molecule, a total of two NADH and four ATP molecules are formed in the energy-generating phase.



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GLYCOLYSIS



749



• Coenzyme NAD+ is a biological oxidizing agent that converts C H bonds to C O

bonds. In the process, NAD+ is reduced to NADH + H+.

• The phosphorylation of ADP requires energy and forms ATP, a high-energy nucleoside

triphosphate.

• The hydrolysis of ATP releases energy and forms ADP.



24.3A THE STEPS IN GLYCOLYSIS

The specific steps and all needed enzymes in glycolysis are shown in Figures 24.2–24.4.



Glycolysis: Steps [1]–[3]

Glycolysis begins with the phosphorylation of glucose to form glucose 6-phosphate (Figure 24.2).

This energetically unfavorable reaction is coupled with the hydrolysis of ATP to ADP to make the

reaction energetically favorable. Isomerization of glucose 6-phosphate to fructose 6-phosphate

takes place with an isomerase enzyme in step [2]. Phosphorylation in step [3], an energy-absorbing

reaction, can be driven by the hydrolysis of ATP, yielding fructose 1,6-bisphosphate.





FIGURE 24.2 Glycolysis: Steps [1]–[3]

CH2OH

O



H



H

OH



OH



H



OH



H

H

OH

glucose

ATP



hexokinase



ADP



1



Phosphorylation



2



Isomerization



O

−O



P



O



O−



H

OH



CH2



P

O



H

OH



O



CH2

O



H



OH



H

OH



=



H



H



OH



H



OH

H



H



H

OH

glucose 6-phosphate



OH



phosphohexose

isomerase

P



O



CH2



CH2OH



O



H



HO



H



OH



OH

H

fructose 6-phosphate

ATP



phosphofructokinase



P



O



CH2

H



ADP

CH2



O



3



Phosphorylation



O



P



HO



H



OH



OH

H

fructose 1,6-bisphosphate



• All –PO32– groups in glycolysis are abbreviated as



P .



• The energy from two ATP molecules is used for phosphorylation in steps [1] and [3].



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750



CARBOHYDRATE, LIPID, AND PROTEIN METABOLISM



• Overall, the first three steps of glycolysis add two phosphate groups and isomerize a sixmembered glucose ring to a five-membered fructose ring.

• The energy stored in two ATP molecules is utilized to modify the structure of glucose for

the later steps that generate energy.



PROBLEM 24.3



What type of isomers—constitutional isomers or stereoisomers—do glucose 6-phosphate and

fructose 6-phosphate represent? Explain your choice.



Glycolysis: Steps [4]–[5]

Cleavage of the six-carbon chain of fructose 1,6-bisphosphate forms two three-carbon products—

dihydroxyacetone phosphate and glyceraldehyde 3-phosphate—as shown in Figure 24.3. These

two products have the same molecular formula but a different arrangement of atoms; that is, they

are constitutional isomers of each other. Since only glyceraldehyde 3-phosphate continues on in

glycolysis, dihydroxyacetone phosphate is isomerized to glyceraldehyde 3-phosphate in step [5],

completing the energy-investment phase of glycolysis.

In summary:

• The first phase of glycolysis converts glucose to two molecules of glyceraldehyde

3-phosphate.

• The energy from two ATP molecules is utilized.



PROBLEM 24.4



Identify the type of carbonyl groups present in dihydroxyacetone phosphate and glyceraldehyde

3-phosphate. Classify the OH groups in each compound as 1o, 2o, or 3o.



PROBLEM 24.5



As we learned in Section 23.3, the hydrolysis of ATP to ADP releases 7.3 kcal/mol of energy.

If the coupled reaction, fructose 6-phosphate + ATP → fructose 1,6-bisphosphate + ADP,

releases 3.4 kcal/mol of energy, how much energy is required for the phosphorylation of

fructose 6-phosphate?

fructose 6-phosphate + HPO42–







fructose 1,6-bisphosphate + H2O



FIGURE 24.3 Glycolysis: Steps [4] and [5]

P



O



CH2



fructose 1,6-bisphosphate



O



CH2



O



H



P



HO



H



OH

OH



H



This bond is broken.

aldolase



4



Cleavage



O

P



O



CH2



C



CH2OH



+



P



O



dihydroxyacetone

phosphate



CH2



OH



O



CH



C



glyceraldehyde

3-phosphate



H

Two molecules of glyceraldehyde

3-phosphate are formed from one

glucose molecule.



triose phosphate isomerase

5



Isomerization



Cleavage of a carbon–carbon bond and isomerization form two molecules of glyceraldehyde

3-phosphate from glucose, completing the energy-investment phase of glycolysis.



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