CHM 102 Chapter 18

Chapter

Eighteen

Metabolism

High = 106

Median = 82

Average = 77

EXAM 3 RESULTS

Copyright © Houghton Mifflin Company. All rights reserved.

11 –2

The Final Exam

The final exam will be held:

Wednesday March 14, 2007

8:30-10:30 am

In this room

There will be 75 questions. The exam will cover all the material in the course, but with somewhat greater emphasis on Chapter 18 than on the other chapters.


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“Metabolism” refers to the very large number of chemical reactions that occur in living organisms


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Types of Metabolic Reactions

• Thousands of different reactions occur in our cells: we shall only study a small number of these reactions.

• We use food for energy and also to build up our body parts.

• Over 40 years an average adult processes

6 tons of food and 10,000 gallons of water.

• Metabolic reactions are of two general types: catabolic (breaking down) and anabolic (building up/synthesizing).


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Catabolic reactions (breaking down chemicals) usually release energy

Anabolic reactions (synthesizing substances) generally consume energy.

A metabolic pathway refers to a series of reactions intended to convert one substance into another.

The path may be linear or cyclic.

Linear : A → B → C → D

Cyclic : A → B

↑ ↓

D ← C


11 –6

The Structures of Cells

■ Bacteria are “prokaryotic” organisms and their cells lack a nucleus.

■ All higher organisms have “eukaryotic” cells that have a nucleus.

Schematic of a eukaryotic cell

Mitochondria are the main energyproducing organelles


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ATP is the “energy currency” of the cell

Hydrolysis of ATP releases energy and inorganic phosphate (P i

)


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Hydrolysis of ATP releases energy

Breaking the phosphate-phosphate bonds releases energy:


11 –9

Three Important Coenzymes

Flavin Adenine Dinucleotide = FAD

Ribitol is a reduced form of ribose

Flavin is a threering structure

The key idea is that FAD can be readily oxidized and reduced:


11 –10

Nicotinamide Adenine Dinucleotide = NAD

NAD has the same sort of structure as

FAD

Nicotinamide is a single-ring heterocyclic compound

NAD also can be oxidized and reduced:


11 –11

Coenzyme A

CoA transfers acetyl groups

O

║ acetyl group = CH

3

-C --


11 –12

Biochemical Energy Production

Four Stages:

Stage 1 : Digestion begins in the mouth and continues in the stomach and small intestine. (Proteins, lipids, polysaccharides are broken down into their subunits: amino acids, fatty acids, sugars.)

Stage 2 : The small molecules are broken down further, mainly into acetyl groups joined to CoA, i.e., as acetyl CoA ..

Stage 3 : The citric acid cycle occurs in the mitochondria.

Acetyl CoA is taken in , yielding energy , NADH and FADH

2

, and CO

2

.

Stage 4 : Electron transport and oxidative phosphorylation occur, also in the mitochondria. NADH

2 and electrons. ATP is produced . O

2 and FADH

2 supply H from breathing is

+ s converted to H

Copyright

2

O.

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The four stages of energy production


11 –14

■ Breakdown of foods to smaller compounds

■ Further breakdown to two-carbon units bonded to CoA, as acetyl CoA

■ Acetyl CoA is oxidized to produce

CO

2 and NADH and

FADH

2

■ Production of ATP is aided by NADH and

FADH

2

, taking up O

2


11 –15

The Citric Acid Cycle


11 –16

Overview of the Citric Acid Cycle

In Stage 1 of digestion the ingested foods (carbohydrates, fats, and proteins) were broken down into their smaller parts (sugars, fatty acids, etc.). In Stage 2 these compounds were further broken down to 2-carbons acetyl units bonded to CoA. These units now enter the CA Cycle, one at a time.

The Citric Acid Cycle (CAC) is Stage 3 .

In a series of eight steps (1) two CO

2 molecules will be released, (2) a molecule of CoA-SH will be regenerated, (3) three NADHs and one FADH

2 will be generated (from NAD + and FAD), and (4) one high-energy compound (GTP) will be created.

We will examine the eight steps in order to get an idea of how this works.


11 –17

Other names for the Citric Acid Cycle

Note that the Citric Acid Cycle (CAC) is sometimes called the “ Tricarboxylic Acid Cycle ” (TCA) (because citric acid has three COO groups)

The CAC is also sometimes called the “ Krebs Cycle ” in honor of the British biochemist Sir Hans Krebs, who worked out many of the steps in the cycle. Krebs shared the 1953 Nobel Prize for Physiology or Medicine for this work.


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This cycle takes place mainly in the mitochondrial matrix


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Step 1. Formation of Citrate

Acetyl CoA enters the cycle and combines with the 4-carbon compound oxaloacetate:

This hydrolysis step is catalyzed by the enzyme

citrate synthase. It yields a 6-carbon compound, citrate, and releases acetyl CoA-SH to be used again.


11 –20

Steps 2 and 3

Step 2: The citrate is isomerized to isocitrate, under the influence of the enzyme aconitase.

Step 3: The enzyme isocitrate dehydrogenase converts isocitrate to α-ketogluterate, converting NAD + to NADH and releasing a molecule of CO

2

.


11 –21

Step 4

Step 4: The α-ketogluterate is converted to succinyl, generating another NADH and another CO

2

. CoA-SH enters and attaches to the 4-carbon succinyl.

Note that another enzyme is employed.


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Step 5

Step 5: CoA-SH is regenerated, and a new compound,

GDP (similar to ADP) is phosphorylated to GTP.

Note that another enzyme is employed.


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Steps 6, 7, and 8

These steps involve some familiar organic reactions of types that we have seen earlier in the course.

Note that here too, enzymes are employed.


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Step 6

In this step an alkane is dehydrogenated to form an alkene. The hydrogens go onto FAD to form FADH

2

:

Here the enzyme succinate dehydrogenase is used..


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Step 7

The fumerate from Step 6 adds a water molecule at its double bond to produce L-malate.

The enzyme fumerase is used.


11 –26

Step 8

The L-malate from Step 7 is oxidized to form oxaloacetate and NADH. Remember, we started the whole cycle when oxaloacetate reacted with acetyl CoA.

The enzyme malate dehydrogenase is used.


11 –27

Summary of the Citric Acid Cycle



We began the cycle with oxaloacetate (a 4-carbon compound) and added acetyl CoA (CH

3

-C=O-S-CoA).



In going around the cycle a series of eight steps occurred, yielding the following:

2CO

2

, CoA-SH, 3NADH, 2H + , FADH, and GTP



Thus the two carbons of the acetyl have been converted to CO

2

, a high-energy compound (GTP) has been produced, and the carrier CoA-SH has been released.



Note that at the end the original oxaloacetate has been regenerated to start the cycle again.

Different enzymes guided each step.


11 –28

Further Comments on the Citric Acid Cycle

 The “fuel” of the cycle is acetyl CoA , from the breakdown of foodstuffs.



The reactions take place mainly in the mitochondrial matrix .



Four of the steps involve oxidation or reduction . The oxidizing agents are NAD + (three times) and FAD (once).



Four B vitamins are used in the cycle: riboflavin (in

FAD and the α-ketoglutarate complex), nicotinamide (in

NAD + ), pantothenic acid (in CoA-SH), and thiamin (in the

α-ketoglutarate complex).

Different enzymes guided each step.


11 –29

The Electron Transport Chain

We have now gone through three of the four stages of digestion of foodstuffs. The “Electron Transport Chain” and “Oxidative Phosphorylation” comprise the fourth stage.

The Electron Transport Chain involves a series of reactions in which electrons and hydrogen ions from

NADH and FADH

2 are passed along through a chain of carriers, eventually reacting with O

2 to form H

2

O.

These reactions take place mainly in enzyme complexes located in the mitochondrial inner membrane. They lead to the production of ATP molecules.


11 –30

The Essential Details

The steps in this chain are rather complicated and we don’t need to know all the details.

We should know that electrons are passed along through a chain of intermediate “carriers”:

A cytochrome is a heme-containing protein that undergoes reversible oxidation and reduction of its iron atoms: Iron goes between its Fe +3 and Fe +2 states.


11 –31

Recall the Heme Group

The action occurs at the iron atom in the center


11 –32

Review Sessions



In class next Monday – We will review material for the

Final Exam. Come prepared to ask questions


11 –33

The carriers for the Electron Transport Chain are located in the mitochondrial inner membrane

Coenzyme Q and cytochrome c are mobile —they can move between the fixed enzyme complexes.


11 –34

In the electron Transport Chain

Oxidation and Reduction

Reactions are Coupled


11 –35

One component is oxidized and the other is reduced

For example:

And among the cytochromes:


11 –36

A second function of the Electron

Transport Chain is to pump protons

Note that it takes energy to pump protons from a region of low concentration to one of high concentration.


11 –37

The net result of the Electron

Transport Chain is that molecular oxygen is reduced to water

O

2

+ 4H

+

+ 4e

-

→ 2H

2

O

In the chain carriers first are oxidized (accept electrons) and are then reduced (lose electrons to the next carrier).

About 95% of all the oxygen used by cells serves as the final electron acceptor in the ETC.

The enzyme complex containing cytochromes a and a3 is called cytochrome oxidase. Its structure includes both iron and copper. Electrons are transferred from copper to iron to oxygen.


11 –38

Oxidative Phosphorylation

This is the process in which energy released by the ETC is used to make ATP from ADP

Pumping the protons to a region of higher H + concentration creates an electrochemical gradient. This gradient drives a flow of H + through enzyme complexes called

ATP synthases. These complexes catalyze the production of ATP from ADP.


11 –39


11 –40

Energy Bookkeeping

As a result of all these reactions and shuffling of electrons, ATP is produced.

Recall that every acetyl CoA entering the CAC leads to three NADH, one FADH

2

, and one GTP. When electrons released from these products go through the ETC and oxidative phosphorylation, they help create ATP.

Every NADH yields 2.5 ATPs

Every FADH

2 yields 1.5 ATPs

Each GTP yields 1 ATP

Thus 3x2.5 = 7.5

Thus 1x2.5 = 1.5

Thus 1x1 =

Total =

1.0

10.0

Conclusion: Every acetyl CoA that enters the citric acid cycle results in 10 ATPs created.


11 –41

Glycolysis

Glycolysis refers to the metabolic pathway in which glucose (six carbons) is converted to two molecules of pyruvate (3 carbons each).

Here we go back to Stage 2 and consider just how acetyl

CoA is generated from glucose. (We will not consider how other compounds are converted to acetyl CoA.)

There are two steps:

Glucose —> 2 pyruvate (glycolysis)

Pyruvate —> acetyl CoA

This is an anaerobic pathway. (It doesn’t use oxygen.)


11 –42

Glycolysis (continued)

This is a ten-step process, each step enzymecatalyzed.



In steps 1 and 3 phosphate groups from ATP are attached to the sugars, and in step 6 two more phosphate are attached with the aid of NAD + .



In steps 7and 10 ATPs are produced (total = 4)



Two ATPs are consumed and four are produced. The net gain from glycolysis is therefore 4-2 = 2 ATPs for each glucose entering the process.


11 –43

Glucose enters and is phosphorylated in step 1.

A second phosphorylation from ATP in step 3.

Two glyceraldehyde 3phosphates are created.

Two ATPs are produced in step 7.

Two more ATPs are produced in step 10.


11 –44

Step 1: Glucose is phosphorylated

The (P) is a shorthand for a PO

3

-2 unit. Kinase enzymes catalyze phosphate transfer reactions.


11 –45

Step 2: Isomerization of the glucose 6-phosphate

Step 3: A second phosphate is attached.

Steps 4 and 5: The 6-carbon sugar is converted to two 3-carbon sugars.

Step 6: Another phosphate is attached to each 3carbon compound. Now each one has two (P)s.

Step 7: A phosphate is removed from each 3-carbon compound to form an ATP molecule.


11 –46

Glycolysis (continued)

Step 7 (cont.): The step just shown is an example of substrate-level phosphorylation —direct transfer of a

(P) from a compound to ADP to form ATP.

(This differs from oxidative phosphorylation, where a free phosphate ion in solution (P i

) is attached to ADP to form ATP.)

Step 8: The compound is rearranged (isomerized).

Step 9: A water molecule is removed to yield a C=C double bond with the phosphate group attached to it .

Step 10: The phosphate group is split off and attached to ADP, thus forming ATP.


11 –47

Glycolysis: The Net Reaction

The net overall equation for glycolysis is:

Glucose + 2 NAD + + 2 ADP + 2P i

—>

2 Pyruvate + 2 NADH + 2 ATP + 2H + + 2H

2

O

There is a net gain of two ATPs, and two pyruvates are formed.


11 –48

So What Happens to the Pyruvate?

It depends on conditions :


11 –49

Aerobic Conditions: Formation of Acetyl CoA

Under oxygen-rich (aerobic) conditions the reaction of a glucose molecule yields the following:

Glucose + 2 ADP + 2 P i

+ 4 NAD + + 2 CoA —>

2 acetyl CoA + 2 CO

2

+ 2 ATP + 4 NADH + 4H + + 2 H

2

O

The acetyl CoAs can now go into the Citric Acid Cycle and the Electron Transport Chain.


11 –50

Anaerobic Conditions: Reduction to Lactate

In the absence of air, pyruvate is reduced to lactate in humans and many other organisms.

Accumulation of lactate in your muscles and blood causes fatigue after strenuous exercise.

The net reaction in this case is :


—> 2 Lactate + 2 ATP + 2 H

2

O

Anaerobic organisms are energy-poor.


11 –51

Anaerobic Conditions: Reduction to Ethanol

Some anaerobic organisms —such as yeast—can take a different path and ferment the glucose to ethanol.

The overall reaction in this case is:


—>

2 Ethanol + 2 ATP + 2 CO

2

+ 2 H

2

This pathway is used in the productionof beer, wine, and other alcoholic drinks.

It also causes bread to rise as CO2 bubbles form during the baking process.


11 –52

Aerobic Conditions: The Overall Story

Here’s the tally for the complete oxidation of one molecule of glucose.

Glycolysis (glucose –> 2 pyruvates) 2 ATP

Oxidation of 2 Pyruvates 0 ATP

Citric Acid Cycle

ETC and Ox. Phosphorylation

2 ATP

26 ATP

Net yield of ATP = 30 ATP

Compare this with the yield of just 2 ATP for anaerobes.


11 –53

What you absolutely must know from Chapter 18:

￭

First, appreciate that this chapter treats metabolism in great detail, and you don’t need to know every chemical and every reaction. BUT, you do need to understand the general features of metabolism as described below.

￭ Understand that “metabolism” includes tens of thousands of reactions in the human body. We just scratch the surface in our study.

￭ Understand that there are two broad categories of reactions: catabolic (“breaking down”, energy-releasing) and anabolic (“building up”, energy consuming).

￭ Chapter 18 deals entirely with the first category —the breakdown of food stuffs to yield energy.


11 –54

What you absolutely must know from Chapter 18 (cont.):

￭ Understand the structure of a typical cell (Fig. 18.2), noting especially the ribosomes and the mitochondria.

Understand the structure of a mitochondrion (Fig. 18.3).

￭ Understand the structures of AMP, ADP, and ATP.

Appreciate that the breaking of the terminal phosphatephosphate bond of ATP releases a great deal of energy

(producing ADP plus P i

).

￭ Understand that there are three key coenzymes needed for our study of food breakdown: FAD, NAD + , and

Coenzyme A. Know that the first two act in oxidationreduction roles, and be able to identify their oxidized and reduced forms. Understand that Coenzyme A carries acetyl groups into the CAC. Know what a “coenzyme” is.

￭ Understand that FAD and NAD + are dinucleotides.


11 –55


￭ Understand what an acetyl group is and how it is bonded to

CoA.

￭ Understand what happens in each of the four stages of biochemical energy production. Know where each takes place.

￭ Regarding the Citric Acid Cycle: understand (1) where it takes place, (2) that two-carbon units enter the cycle as acetyl

CoA units, which combine with oxaloacetate, (3) what ingredients are generated in the cycle (e.g., 2 CO

2

, 2 ATP, etc.), (4) that there are 8 steps, each guided by a different enzyme, and (5) that CoA is released in step 1 and oxaloacetate is regenerated in the final step.

￭ You don’t need to know the names of every specific enzyme, but you should understand what the major types of enzymes do (e.g., isomerases, dehydrogenases, kinases…)

11 –56


￭ Understand the overall summary of the CAC (page 513), and appreciate that this cycle is sometimes also called the

“Tricarboxylic Acid Cycle” or the “Krebs Cycle” (note on page 510).

￭ Understand that steps 6-8 in the CAC involve ordinary organic reactions of types we studied earlier. Be prepared to recognize the type of reaction involved.

￭ Regarding the Electron Transport Chain: understand (1) where it takes place, and (2) that it involves a series of oxidation-reduction reactions in which electrons and hydrogen ions from NADH and FADH

2 eventually reacting with O

2 are passed along, to produce H

2

O.

￭ You should know generally what a “heme” group looks like, and what a “cytochrome” is.


11 –57


￭ Regarding oxidative phosphorylation: understand (1) where it takes place, and (2) that it involves capturing the energy from a flow of protons through enzyme complexes called ATP synthases to produce ATPs. Appreciate that the electrochemical gradient causing the proton flow was generated by enzymes fixed in the mitochondrial cell membraes, which pump protons to regions of higher concentration (see Figs. 18.12 and 18.13).

￭ You should appreciate that ATP is the principal energycarrying molecule in the cell, and that its hydrolysis is utilized to supply energy for a range of activities such as muscle contraction, nutrient transport, and the synthesis of bodily components.

￭ Appreciate that the “Common Metabolic Pathway” refers to the sum of the reactions that occur in the Citric Acid Cycle, the Electron Transport Chain, and Oxidative Phosphorylation.


11 –58


￭ Appreciate that most biochemical reactions consist of coupled reactions in which one compound is oxidized while another is reduced.

￭ Understand that “glycolysis” refers to the process in which the sugar glucose (C

6

) is transformed into two molecules of pyruvate (two C

3

). Appreciate that this is accomplished in a series of 10 steps, and generates 2 ATPs (net).

￭ Understand that there are three possible metabolic routes for the pyruvate generated in glycolysis: (1) aerobic oxidation via the CAC, ETC, and OP, (2) anaerobic conversion to lactic acid (lactate), or (3) anaerobic fermentation leading to ethanol.

￭ Appreciate that lactic acid is what causes fatigue in muscles and that fermentation is used in making beer, wine and other beverages.


11 –59


￭ Appreciate the importance of the energy bookkeeping information shown on page 530 —that aerobic metabolism of a glucose molecule yields 30 ATPs, whereas anaerobic metabolism yields just 2 ATPs.

￭ Understand that as a result of the above difference only higher (aerobic) organisms are efficient enough to sit around and think and study organic chemistry and biochemistry.

￭ Appreciate that the aerobic metabolism reactions described above constitute “ respiration ”, taking in O

2 to oxidize foodstuffs, thereby capturing energy (as ATPs) and releasing CO

2 and H

2

O. Understand that respiration is just the reverse of photosynthesis, in which green plants take in

CO

2 and H

2

O and use energy from the sun to synthesize sugars, releasing O

2 in the process.


11 –60

To Do List

• Read chapter 18!!

• Do additional problems

•

Do practice test T/F

•

Do practice test MC

• Review Lecture notes for

Chapter Eleven


11 –61

CHM 102 Chapter 18

Chapter

Eighteen

Metabolism

EXAM 3 RESULTS

“Metabolism” refers to the very large number of chemical reactions that occur in living organisms

Types of Metabolic Reactions

The Structures of Cells

The Electron Transport Chain

The Essential Details

Recall the Heme Group

Review Sessions

In the electron Transport Chain

Oxidation and Reduction

Reactions are Coupled

One component is oxidized and the other is reduced

A second function of the Electron

Transport Chain is to pump protons

The net result of the Electron

Transport Chain is that molecular oxygen is reduced to water

O

+ 4H

+ 4e

→ 2H

O

Oxidative Phosphorylation

This is the process in which energy released by the ETC is used to make ATP from ADP

Energy Bookkeeping

Glycolysis

Glycolysis (continued)

Step 1: Glucose is phosphorylated

Glycolysis (continued)

Glycolysis: The Net Reaction

So What Happens to the Pyruvate?

Related documents

Products

Support

CHM 102 Chapter 18

Chapter

Eighteen

Metabolism

EXAM 3 RESULTS

“Metabolism” refers to the very large number of chemical reactions that occur in living organisms

Types of Metabolic Reactions

The Structures of Cells

The Electron Transport Chain

The Essential Details

Recall the Heme Group

Review Sessions

In the electron Transport Chain

Oxidation and Reduction

Reactions are Coupled

One component is oxidized and the other is reduced

A second function of the Electron

Transport Chain is to pump protons

The net result of the Electron

Transport Chain is that molecular oxygen is reduced to water

O

+ 4H

+ 4e

→ 2H

O

Oxidative Phosphorylation

This is the process in which energy released by the ETC is used to make ATP from ADP

Energy Bookkeeping

Glycolysis

Glycolysis (continued)

Step 1: Glucose is phosphorylated

Glycolysis (continued)

Glycolysis: The Net Reaction

So What Happens to the Pyruvate?

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