Download Chapter Eleven - Wright State University

Chapter
Eighteen
Metabolism
EXAM 3 RESULTS
High = 106
Median = 82
Average = 77
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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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11–3
“Metabolism” refers to the very large
number of chemical reactions that
occur in living organisms
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11–4
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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11–5
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
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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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11–7
ATP is the “energy currency” of the cell
Hydrolysis of ATP releases energy and inorganic
phosphate (Pi)
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Hydrolysis of ATP releases energy
Breaking the phosphate-phosphate bonds releases energy:
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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:
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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:
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11–11
Coenzyme A
CoA transfers acetyl
groups
O
║
acetyl group = CH3-C -Copyright © Houghton Mifflin Company. All rights reserved.
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 FADH2,
and CO2.
Stage 4: Electron transport and oxidative phosphorylation
occur, also in the mitochondria. NADH2 and FADH2 supply H+s
and electrons. ATP is produced. O2 from breathing is
converted to H2O.
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The four
stages
of energy
production
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■ Breakdown of foods
to smaller compounds
■ Further breakdown
to two-carbon units
bonded to CoA, as
acetyl CoA
■ Acetyl CoA is
oxidized to produce
CO2 and NADH and
FADH2
■ Production of ATP is
aided by NADH and
FADH2, taking up O2
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11–15
The Citric Acid Cycle
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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 CO2 molecules will be
released, (2) a molecule of CoA-SH will be regenerated, (3)
three NADHs and one FADH2 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.
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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.
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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 CO2.
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11–21
Step 4
Step 4: The α-ketogluterate is converted to succinyl,
generating another NADH and another CO2. 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 FADH2:
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.
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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.
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11–27
Summary of the Citric Acid Cycle
 We began the cycle with oxaloacetate (a 4-carbon
compound) and added acetyl CoA (CH3-C=O-S-CoA).
 In going around the cycle a series of eight steps
occurred, yielding the following:
2CO2, CoA-SH, 3NADH, 2H+, FADH, and GTP
 Thus the two carbons of the acetyl have been
converted to CO2, 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.
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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.
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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 FADH2 are passed along through a chain of
carriers, eventually reacting with O2 to form H2O.
These reactions take place mainly in enzyme complexes
located in the mitochondrial inner membrane. They lead
to the production of ATP molecules.
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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.
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11–31
Recall the Heme Group
The action occurs at the iron atom in the center
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11–32
Review Sessions
 In class next Monday – We will review material for the
Final Exam. Come prepared to ask questions
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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.
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11–34
In the electron Transport Chain
Oxidation and Reduction
Reactions are Coupled
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One component is oxidized and
the other is reduced
For example:
And among the cytochromes:
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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.
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The net result of the Electron
Transport Chain is that molecular
oxygen is reduced to water
O2 + 4H+ + 4e- → 2H2O
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.
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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.
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11–39
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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 FADH2, 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 FADH2 yields 1.5 ATPs
Each GTP yields 1 ATP
Thus 3x2.5 = 7.5
Thus 1x2.5 = 1.5
Thus 1x1 = 1.0
Total =
10.0
Conclusion: Every acetyl CoA that enters the
citric acid cycle results in 10 ATPs created.
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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.)
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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.
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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.
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Step 1: Glucose is phosphorylated
The (P) is a shorthand for a PO3-2 unit. Kinase enzymes
catalyze phosphate transfer reactions.
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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.
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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 (Pi) 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.
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11–47
Glycolysis: The Net Reaction
The net overall equation for glycolysis is:
Glucose + 2 NAD+ + 2 ADP + 2Pi —>
2 Pyruvate + 2 NADH + 2 ATP + 2H+ + 2H2O
There is a net gain of two ATPs, and two pyruvates are
formed.
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So What Happens to the Pyruvate?
It depends on conditions:
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Aerobic Conditions: Formation of Acetyl CoA
Under oxygen-rich (aerobic) conditions the reaction of a
glucose molecule yields the following:
Glucose + 2 ADP + 2 Pi + 4 NAD+ + 2 CoA —>
2 acetyl CoA + 2 CO2 + 2 ATP + 4 NADH+ 4H+ + 2 H2O
The acetyl CoAs can now go into the Citric Acid Cycle
and the Electron Transport Chain.
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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 :
Glucose + 2 ADP + 2 Pi —> 2 Lactate + 2 ATP + 2 H2O
Anaerobic organisms are energy-poor.
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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:
Glucose + 2 ADP + 2 Pi —>
2 Ethanol + 2 ATP + 2 CO2 + 2 H2
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.
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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
2 ATP
ETC and Ox. Phosphorylation
26 ATP
Net yield of ATP = 30 ATP
Compare this with the yield of just 2 ATP for anaerobes.
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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.
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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 Pi).
￭ 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.
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11–55
What you absolutely must know from Chapter 18 (cont.):
￭ 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 CO2, 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…)
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so
that
you
their actions in examples.
What you absolutely must know from Chapter 18 (cont.):
￭ 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 FADH2 are passed along,
eventually reacting with O2 to produce H2O.
￭ You should know generally what a “heme” group looks like,
and what a “cytochrome” is.
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11–57
What you absolutely must know from Chapter 18 (cont.):
￭ 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.
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What you absolutely must know from Chapter 18 (cont.):
￭ 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 (C6) is transformed into two molecules of
pyruvate (two C3). 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.
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11–59
What you absolutely must know from Chapter 18 (cont.):
￭ 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 O2 to
oxidize foodstuffs, thereby capturing energy (as ATPs) and
releasing CO2 and H2O. Understand that respiration is just
the reverse of photosynthesis, in which green plants take in
CO2 and H2O and use energy from the sun to synthesize
sugars, releasing O2 in the process.
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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
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