Chapter 4
Lecture
PowerPoint
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2
Hole’s Human Anatomy
and Physiology
Twelfth Edition
Shier w Butler w Lewis
Chapter
4
Cellular Metabolism
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
3
Important Points in Chapter 4:
Outcomes to be Assessed
4.1: Introduction
 Define metabolism.
 Explain why protein synthesis is important.
4.2: Metabolic Processes
 Compare and contrast anabolism and catabolism.
 Define dehydration synthesis and hydrolysis.
4.3: Control of Metabolic Reactions
 Describe how enzymes control metabolic reactions.
 List the basic steps of an enzyme-catalyzed reaction.
 Define active site.
4
Important Points in Chapter 4:
Outcomes to be Assessed
 Define a rate-limiting enzyme and indicate why it is important in a
metabolic pathway.
4.4: Energy for Metabolic Reactions
 Explain how ATP stores chemical energy and makes it available to a
cell.
 State the importance of the oxidation of glucose.
4.5: Cellular Respiration
 Describe how the reactions and pathways of glycolysis, the citric
acid cycle, and the electron transport chain capture the energy in
nutrient molecules.
 Discuss how glucose is stored, rather than broken down.
5
Important Points in Chapter 4:
Outcomes to be Assessed
4.6: Nucleic Acids and Protein Synthesis
 Define gene and genome.
 Describe the structure of DNA, including the role of complementary
base pairing.
 Describe how DNA molecules replicate.
 Define genetic code.
 Compare DNA and RNA.
 Explain how nucleic acid molecules (DNA and RNA) carry genetic
information.
 Define transcription and translation.
 Describe the steps of protein synthesis.
6
Important Points in Chapter 4:
Outcomes to be Assessed
4.7: Changes in Genetic Information
 Compare and contrast mutations and SNPs.
 Explain how a mutation can cause a disease.
 Explain two ways that mutations originate.
 List three types of genetic changes.
 Discuss two ways that DNA is protected against mutation.
7
4.1: Introduction
• Metabolic processes – all chemical reactions that occur
in the body
There are two (2) types of metabolic reactions:
• Anabolism
• Larger molecules
are made from
smaller ones
• Requires energy
• Catabolism
• Larger molecules
are broken down into
smaller ones
• Releases energy
8
4.2: Metabolic Processes
• Consists of two processes:
• Anabolism
• Catabolism
9
Anabolism
• Anabolism provides the materials needed for cellular
growth and repair
• Dehydration synthesis
• Type of anabolic process
• Used to make polysaccharides, triglycerides, and proteins
• Produces water
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CH2OH
CH2OH
O
H
O
H
H
CH2OH
H
O
H
H
CH2OH
H
O
H
H
H
H
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Monosaccharide
+
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H
OH
Monosaccharide
OH
HO
OH
H
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OH
O
Disaccharide
OH
H
H
OH
OH
+
Water
10
Anabolism
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H
H
H
O
C
OH
HO
C
(CH2)14 CH3
H
O
C
O
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(CH2)14 CH3
H
H
C
O
C
(CH2)14 CH3
H
+
Glycerol
3 fatty acid molecules
+
Fat molecule (triglyceride)
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3 water
molecules
Peptide
bond
H
H
N
H
C
C
R
Amino acid
H
H
O
N
O
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+
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+
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11
Catabolism
• Catabolism breaks down larger molecules into smaller ones
• Hydrolysis
• A catabolic process
• Used to decompose carbohydrates, lipids, and proteins
• Water is used to split the substances
• Reverse of dehydration synthesis
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CH2OH
CH2OH
O
H
O
H
H
CH2OH
H
O
H
H
CH2OH
H
O
H
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OH
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Disaccharide
OH
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OH
+
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12
Water
Catabolism
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H
H
H
O
C
OH
HO
C
(CH2)14 CH3
H
O
C
O
O
H
C
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H
C
O
C
(CH2)14 CH3
H
+
Glycerol
3 fatty acid molecules
+
Fat molecule (triglyceride)
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3 water
molecules
Peptide
bond
H
H
N
H
C
C
R
Amino acid
H
H
O
N
O
H
H
+
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H
O
C
R
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N
O
H
H
H
O
C
C
R
R
N
C
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H
Dipeptide molecule
O
C
OH
H2O
+
Water
13
4.3: Control of Metabolic
Reactions
• Enzymes
• Control rates of metabolic reactions
• Lower activation energy needed to start reactions
• Most are globular proteins with specific shapes
• Not consumed in chemical reactions
• Substrate specific
• Shape of active site determines substrate
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Substrate molecules
Product molecule
Active site
Enzyme
molecule
(a)
Enzyme-substrate
complex
(b)
(c)
Unaltered
enzyme
molecule
14
Animation: How Enzymes Work
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15
Enzyme Action
• Metabolic pathways
• Series of enzyme-controlled reactions leading to formation of a
product
• Each new substrate is the product of the previous reaction
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Substrate
1
Enzyme A
Substrate
2
Enzyme B
Substrate
3
Enzyme C
Substrate
4
Enzyme D
• Enzyme names commonly:
• Reflect the substrate
• Have the suffix – ase
• Examples: sucrase, lactase, protease, lipase
Product
16
Cofactors and Coenzymes
• Cofactors
• Make some enzymes active
• Non-protein component
• Ions or coenzymes
• Coenzymes
• Organic molecules that act as cofactors
• Vitamins
17
Factors That Alter Enzymes
• Factors that alter enzymes:
• Heat
• Radiation
• Electricity
• Chemicals
• Changes in pH
18
Regulation of Metabolic Pathways
• Limited number of regulatory enzymes
• Negative feedback
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Inhibition
Rate-limiting
Enzyme A
Substrate
Substrate
2
1
Enzyme B
Substrate
3
Enzyme C
Substrate
4
Enzyme D
Product
19
4.4: Energy for Metabolic
Reactions
• Energy is the capacity to change something; it is the
ability to do work
• Common forms of energy:
• Heat
• Light
• Sound
• Electrical energy
• Mechanical energy
• Chemical energy
20
ATP Molecules
• Each ATP molecule has three parts:
• An adenine molecule
• A ribose molecule
• Three phosphate molecules in a chain
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P
P
Energy transferred
and utilized by
metabolic reactions
when phosphate bond
is broken
Energy transferred from
cellular respiration used
to reattach phosphate
P
P
P
P
P
21
Release of Chemical Energy
• Chemical bonds are broken to release energy
• We burn glucose in a process called oxidation
22
4.5: Cellular Respiration
•
Occurs in a series of reactions:
1. Glycolysis
2. Citric acid cycle (aka TCA or Kreb’s Cycle)
3. Electron transport system
23
Cellular Respiration
• Produces:
• Carbon dioxide
• Water
• ATP (chemical energy)
• Heat
• Includes:
• Anaerobic reactions (without O2) - produce little ATP
• Aerobic reactions (requires O2) - produce most ATP
24
Glycolysis
• Series of ten reactions
• Breaks down glucose into 2 pyruvic acid molecules
• Occurs in cytosol
• Anaerobic phase of cellular respiration
• Yields two ATP molecules per glucose molecule
Summarized by three main phases or events:
1. Phosphorylation
2. Splitting
3. Production of NADH and ATP
25
Glycolysis
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Event 1 - Phosphorylation
• Two phosphates
added to glucose
• Requires ATP
Event 2 – Splitting (cleavage)
• 6-carbon glucose split
into two 3-carbon
molecules
Glucose
Phase 1
priming
Carbon atom
P Phosphate
2 ATP
2 ADP
Fructose-1,6-diphosphate
P
P
Phase 2
cleavage
Dihydroxyacetone
phosphate
P
Phase 3
oxidation and
formation of
ATP and release
of high energy
electrons
Glyceraldehyde
phosphate
P
P
2 NAD+
4 ADP
2 NADH + H+
4 ATP
2 Pyruvic acid
O2
O2
2 NADH + H+
2 NAD+
2 Lactic acid
To citric acid cycle
and electron transport
chain (aerobic pathway)
26
Glycolysis
Event 3 – Production of NADH and
ATP
• Hydrogen atoms are released
• Hydrogen atoms bind to NAD+
to produce NADH
• NADH delivers hydrogen atoms
to electron transport system if
oxygen is available
• ADP is phosphorylated to
become ATP
• Two molecules of pyruvic acid
are produced
• Two molecules of ATP are
generated
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Glucose
Phase 1
priming
Carbon atom
P Phosphate
2 ATP
2 ADP
Fructose-1,6-diphosphate
P
P
Phase 2
cleavage
Dihydroxyacetone
phosphate
P
Phase 3
oxidation and
formation of
ATP and release
of high energy
electrons
Glyceraldehyde
phosphate
P
P
2 NAD+
4 ADP
2 NADH + H+
4 ATP
2 Pyruvic acid
O2
O2
2 NADH + H+
2 NAD+
2 Lactic acid
To citric acid cycle
and electron transport
chain (aerobic pathway)
27
Anaerobic Reactions
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
• If oxygen is not available:
• Electron transport
system cannot accept
new electrons from
NADH
• Pyruvic acid is
converted to lactic acid
• Glycolysis is inhibited
• ATP production is less
than in aerobic reactions
Glucose
Phase 1
priming
Carbon atom
P Phosphate
2 ATP
2 ADP
Fructose-1,6-diphosphate
P
P
Phase 2
cleavage
Dihydroxyacetone
phosphate
P
Phase 3
oxidation and
formation of
ATP and release
of high energy
electrons
Glyceraldehyde
phosphate
P
P
2 NAD+
4 ADP
2 NADH + H+
4 ATP
2 Pyruvic acid
O2
O2
2 NADH + H+
2 NAD+
2 Lactic acid
To citric acid cycle
and electron transport
chain (aerobic pathway)
28
Aerobic Reactions
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• If oxygen is available:
• Pyruvic acid is used
to produce acetyl CoA
• Citric acid cycle
begins
• Electron transport
system functions
• Carbon dioxide and
water are formed
• 34 molecules of ATP
are produced per each
glucose molecule
Glucose
High energy
electrons (e–) and
hydrogen ions (H+)
2 ATP
Pyruvic acid Pyruvic acid
Cytosol
Mitochondrion
High energy
electrons (e–) and
hydrogen ions (h+)
CO2
Acetyl CoA
Oxaloacetic
acid
Citric acid
High energy
electrons (e–) and
hydrogen ions (H+)
2 CO2
2 ATP
Electron transport chain
32-34 ATP
O2
–
+
2e + 2H
H2O
29
Citric Acid Cycle
• Begins when acetyl CoA
combines with oxaloacetic
acid to produce citric acid
• Citric acid is changed into
oxaloacetic acid through a
series of reactions
• Cycle repeats as long as
pyruvic acid and oxygen are
available
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Pyruvic acid from glycolysis
Cytosol
CO2
Carbon atom
P
NAD+
Phosphate
Mitochondrion CoA Coenzyme A
NADH + H+
Acetic acid
CoA
Acetyl CoA
(replenish molecule)
Oxaloacetic acid
Citric acid
(finish molecule)
(start molecule)
CoA
NADH + H+
NAD+
Malic acid
Isocitric acid
NAD+
• For each citric acid molecule:
• One ATP is produced
• Eight hydrogen atoms are
transferred to NAD+ and
FAD
• Two CO2 produced
Citric acid cycle
CO2
Fumaric acid
NADH + H+
-Ketoglutaric acid
CO2
CoA
NAD+
FADH2
NADH + H+
FAD
Succinic acid
CoA
Succinyl-CoA
ADP + P
ATP
30
Electron Transport System
• NADH and FADH2 carry electrons to the ETS
• ETS is a series of electron carriers located in cristae of
mitochondria
• Energy from electrons transferred to ATP synthase
• ATP synthase catalyzes the phosphorylation of ADP to ATP
• Water is formed
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ADP + P
ATP synthase
ATP
Energy
NADH + H+
Energy
2H+ + 2e–
NAD+
Energy
FADH2
2H+ + 2e–
FAD
Electron transport chain
2e–
2H+
O2
31
H2O
Summary of Cellular
Respiration
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Glucose
Glycolysis
High-energy electrons (e–)
2 ATP
Glycolysis
Cytosol
1 The 6-carbon sugar glucose is broken down in the
cytosol into two 3-carbon pyruvic acid molecules with
a net gain of 2 ATP and release of high-energy
electrons.
Pyruvic acid
Pyruvic acid
Citric Acid Cycle
2 The 3-carbon pyruvic acids generated by glycolysis
enter the mitochondria. Each loses a carbon
(generating CO2 and is combined with a coenzyme to
form a 2-carbon acetyl coenzyme A (acetyl CoA). More
high-energy electrons are released.
High-energy electrons (e–)
CO2
Acetyl CoA
Citric acid
Oxaloacetic acid
Mitochondrion
3 Each acetyl CoA combines with a 4-carbon oxaloacetic
acid to form the 6-carbon citric acid, for which the cycle
is named. For each citric acid, a series of reactions
removes 2 carbons (generating 2 CO2’s), synthesizes
1 ATP, and releases more high-energy electrons.
The figure shows 2 ATP, resulting directly from 2
turns of the cycle per glucose molecule that enters
glycolysis.
Citric acid
cycle
High-energy electrons (e–)
2 CO2
2 ATP
Electron Transport Chain
4
The high-energy electrons still contain most of the
chemical energy of the original glucose molecule.
Special carrier molecules bring the high-energy
electrons to a series of enzymes that convert much of
the remaining energy to more ATP molecules. The
other products are heat and water. The function of
oxygen as the final electron acceptor in this last step is
why the overall process is called aerobic respiration.
Electron
transport
chain
32–34 ATP
2e– and 2H+
O2
H2O
32
Carbohydrate Storage
• Carbohydrate molecules from foods can enter:
• Catabolic pathways for energy production
• Anabolic pathways for storage
33
Carbohydrate Storage
• Excess glucose stored as:
• Glycogen (primarily by liver and muscle cells)
• Fat
• Converted to amino acids
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Carbohydrates
from foods
Hydrolysis
Monosaccharides
Catabolic
pathways
Anabolic
pathways
Energy + CO2 + H2O Glycogen or Fat
Amino acids
34
Summary of Catabolism of
Proteins, Carbohydrates, and Fats
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Food
Proteins
(egg white)
Carbohydrates
Carbohydrates
(toast,
(toast,hashbrowns)
hashbrowns)
Amino acids
Fats
(butter)
Simple sugars
(glucose)
Glycolysis
Glycerol
Fatty acids
ATP
2 Breakdown
Breakdownofofsimple
simple
molecules
moleculestotoacetyl
acetyl
coenzyme
coenzymeAA
accompanied
accompaniedby
by
production
productionofoflimited
limited
ATP
ATPand
andhigh
highenergy
energy
electrons
electrons
Pyruvic acid
Acetyl coenzyme
coenzyme A
A
Acetyl
Citric
acid
cycle
3 Complete oxidation
of acetyl coenzyme A
to H2O and CO2 produces
high energy electrons
(carried by NADH and
FADH2), which yield much
ATP via the electron
transport chain
CO2
ATP
ATP
High
High energy
energy
electrons
electrons carried
carried
by
NADH
by NADH and
and FADH
FADH22
Electron
Electron
transport
transport
chain
chain
1 Breakdown
Breakdown
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large
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ATP
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© Royalty Free/CORBIS.
35
4.6: Nucleic Acids and
Protein Synthesis
• Instruction of cells to synthesize proteins comes from a
nucleic acid, DNA
36
Genetic Information
• Genetic information – instructs cells how to construct
proteins; stored in DNA
• Gene – segment of DNA that codes for one protein
• Genome – complete set of genes
• Genetic Code – method used to translate a sequence of
nucleotides of DNA into a sequence of amino acids
37
4.1 From Science to Technology
DNA Profiling Frees A Prisoner
38
Structure of DNA
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
(a) Hydrogen
bonds
P
C
G
Thymine (T)
Adenine (A)
Cytosine (C)
Guanine (G)
P
P
T
P
P
C
G
P
P
G
P
C
P
A
P
• Two polynucleotide
chains
• Hydrogen bonds hold
nitrogenous bases
together
• Bases pair specifically
(A-T and C-G)
• Forms a helix
• DNA wrapped about
histones forms
chromosomes
G
C
A
Nucleotide strand
G
C
T
C
Segment
of DNA
molecule
G
A
(b)
Globular
histone
proteins
Metaphase
chromosome
(c)
Chromatin
39
Animation: DNA Structure
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40
DNA Replication
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A
• Hydrogen bonds break
between bases
• Double strands unwind
and pull apart
• New nucleotides pair
with exposed bases
• Controlled by DNA
polymerase
T
C
G
G
C
C
G
T
A
Original DNA
molecule
C
G
C
G
A
T
A
C
T
G
A
T
G
C
C
Region of
replication
G
T
T
A
T
A
A
A
A
T
G
C
T
G
A
C
C
T
T
A
T
G
G
G
A
Newly formed
DNA molecules
C
G
A
41
Animation: DNA Replication
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42
4.2 From Science to Technology
Nucleic Acid Amplification
43
Genetic Code
• Specification of the correct sequence of amino acids in a
polypeptide chain
• Each amino acid is represented by a triplet code
44
RNA Molecules
• Messenger RNA (mRNA):
• Making of mRNA (copying of DNA) is transcription
• Transfer RNA (tRNA):
• Carries amino acids to mRNA
• Carries anticodon to mRNA
• Translates a codon of mRNA into an amino acid
• Ribosomal RNA (rRNA):
• Provides structure and enzyme activity for ribosomes
45
RNA Molecules
• Messenger RNA (mRNA):
• Delivers genetic information
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
from nucleus to the cytoplasm
DNA
• Single polynucleotide chain
P
• Formed beside a strand of DNA
P
S
A
U
T
A
G
C
P
S
Direction of “reading” code
• RNA nucleotides are
complementary to DNA
nucleotides (exception – no
thymine in RNA; replaced with
uracil)
RNA
S
P
S
S
P
P
S
S
P
C
G
G
C
P
S
S
P
P
S
46
Animation: Stages of Transcription
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47
Animation: How Translation Works
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48
Protein Synthesis
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DNA
double
helix
Cytoplasm
Nucleus
T A
G C
A T
T A
G C
A T
GC
A T
C G
T A
CG
T A
G C
A T
GC
A T
C G
T A
CG
T A
G C
A T
GC
A T
C G
T A
CG
T A
3 Translation begins as tRNA anticodons
recognize complementary mRNA codons,
thus bringing the correct amino acids into
position on the growing polypeptide chain
6
2 mRNA leaves
the nucleus
and attaches
Messenger
to a ribosome
RNA
A T
U A
G C
G
G C
G
G C
C
C G
T
U A
C
C G
C
C G
G
C G
C G
C
A
A T
A
A T
C
C G
G C
G
G
G C
C G
C
A T
A
G
G C
G
G C
C G
C
U A
T
C
C G
C
C G
A
A T
T
U A
G
G C
A T
A
C
C G
G C
DNA
strands
pulled
apart
T
Amino acids
attached to tRNA
Polypeptide
chain
tRNA molecules
can pick up another
molecule of the
same amino acid
and be reused
G
5 At the end of the mRNA,
the ribosome releases
the new protein
Nuclear
pore
1 DNA
information
is copied, or
transcribed,
into mRNA
following
complementary
base pairing
Messenger
RNA
G C
Transcription
(in nucleus)
DNA
strand
G
C
C
G
A
T
C
G
G
C
C
G
U
C
A
G
4 As the ribosome
moves along the
mRNA, more amino
acids are added
Translation
(in cytoplasm)
Amino acids
represented
A
U
G
G
G
C
U
C
C
G
C
A
A
C
G
G
C
A
G
G
C
Codon 1
Methionine
Codon 2
Glycine
Codon 3
Serine
Codon 4
Alanine
Codon 5
Threonine
Codon 6
Alanine
Codon 7
Glycine
49
Protein Synthesis
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
1
The transfer RNA molecule
for the last amino acid added
holds the growing polypeptide
chain and is attached to its
complementary codon on mRNA.
1
2
Growing
polypeptide
chain
Anticodon
3
4
Next amino acid
5
6
Transfer
RNA
UGCCGU
A U GGGC U C CGC A A CGGCA GGC A A GC GU
1
2
3
4
5
6
7
Codons
2
A second tRNA binds
complementarily to the
next codon, and in doing
so brings the next amino
acid into position on the ribosome.
A peptide bond forms, linking
the new amino acid to the
growing polypeptide chain.
1
2
Growing
polypeptide
chain
Peptide bond
3
4
Next amino acid
5
6
Transfer
RNA
Anticodon
UGCCGU
A U GGGC U C CGC A A CGGCA GGC A A GC GU
1
2
3
2
3
4
5
6
Messenger
RNA
7
Codons
1
3
The tRNA
A molecule that
brought the last amino acid
to the ribosome is released
to the cytoplasm, and will be
used again. The ribosome
moves to a new position at
the next codon on mRNA.
4
5
7
Next
amino acid
6
Transfer
RNA
CGU
A U GGGC U C CGC A A CGGCA GGC A A GC GU
1
2
3
4
5
6
7
Messenger
RNA
Ribosome
1
4
A new tRNA complementary to
the next codon on mRNA brings
the next amino acid to be added
to the growing polypeptide chain.
2
3
4
5
6
7
Next
amino acid
Transfer
RNA
CGU CCG
A U GGGC U C CGC A A CGGCA GGC A A GC GU
1
2
3
4
5
6
7
Messenger
RNA
50
Animation: Protein Synthesis
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51
64 codons code for 20 amino acids
52
4.3 From Science to Technology
MicroRNAs and RNA Interference
53
4.7: Changes in
Genetic Information
• Only about 1/10th of one percent of the human genome
differs from person to person
54
Nature of Mutations
• Mutations – change in genetic
information
• Result when:
• Extra bases are added or
deleted
• Bases are changed
• May or may not change the
protein
Direction of “reading” code
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Code for
glutamic
acid
T
P
Mutation
P
S
P
P
S
A
S
C
P
S
(a)
T
S
T
P
Code for
valine
C
S
(b)
55
56
Protection Against Mutation
• Repair enzymes correct the mutations
57
Inborn Errors of Metabolism
• Occurs from inheriting a mutation that then alters an
enzyme
• This creates a block in an otherwise normal biochemical
pathway
58
4.4 From Science to Technology
The Human Metabolome
59
Quiz 4
Complete Quiz 4 now!
Read Chapter 5.
60