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Chapter 4

Lecture
PowerPoint
Cellular
Metabolism

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4.1: Introduction
• Metabolic processes – all chemical reactions that
occur in the body

There are two (2) types of metabolic reactions:


• Anabolism • Catabolism
• Larger molecules • Larger molecules
are made from are broken down
smaller ones into smaller ones
• Requires energy • Releases energy

2
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 CH2OH CH2OH

O O O O
H H H H H H H H
H H H H
H2O
OH H OH H OH H O OH H
HO OH HO OH HO OH

H OH H OH H OH H OH

Monosaccharide + Monosaccharide Disaccharide + Water

3
Anabolism
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H O H O

H C OH HO C (CH2)14 CH3 H C O C (CH2)14 CH3

O O
H2O
H C OH HO C (CH2)14 CH3 H C O C (CH2)14 CH3 H2O
H2O
O O

H C OH HO C (CH2)14 CH3 H C O C (CH2)14 CH3

H H

Glycerol + 3 fatty acid molecules Fat molecule (triglyceride) + 3 water


molecules
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Peptide
bond

H H H O R
H O H O H O
N C C N C C N C C N C C OH H2O
H O H H O H H
R R R H H

Amino acid + Amino acid Dipeptide molecule + Water


4
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 CH2OH CH2OH

O O O O
H H H H H H H H
H H H H
H2O
OH H OH H OH H O OH H
HO OH HO OH HO OH

H OH H OH H OH H OH

+ +
5
Monosaccharide Monosaccharide Disaccharide Water
Catabolism
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H O H O

H C OH HO C (CH2)14 CH3 H C O C (CH2)14 CH3

O O
H2O
H C OH HO C (CH2)14 CH3 H C O C (CH2)14 CH3 H2O
H2O
O O

H C OH HO C (CH2)14 CH3 H C O C (CH2)14 CH3

H H

Glycerol + 3 fatty acid molecules Fat molecule (triglyceride) + 3 water


molecules
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Peptide
bond

H H H O R
H O H O H O
N C C N C C N C C N C C OH H2O
H O H H O H H
R R R H H

Amino acid + Amino acid Dipeptide molecule + Water


6
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 Enzyme-substrate Unaltered


molecule
7
complex enzyme
(a) (b) (c) molecule
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 Enzyme A Substrate Enzyme B Substrate Enzyme C Substrate Enzyme D


Product
1 2 3 4

• Enzyme names commonly:


• Reflect the substrate
• Have the suffix – ase
• Examples: sucrase, lactase, protease, lipase
8
Cofactors and Coenzymes
• Cofactors
• Make some enzymes active
• Non-protein component
• Ions or coenzymes

• Coenzymes
• Organic molecules that act as
cofactors
• Vitamins

9
Factors That Alter Enzymes
• Factors that alter enzymes:
• Heat
• Radiation
• Electricity
• Chemicals
• Changes in pH

10
Animation:
How Enzymes Work

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11
Regulation of Metabolic
Pathways
• Limited number of regulatory enzymes

• Negative feedback

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Inhibition

Rate-limiting
Substrate Enzyme A Substrate Enzyme B Substrate Enzyme C Substrate Enzyme D
Product
1 2 3 4

12
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

13
ATP Molecules
• Each ATP molecule has three parts:
• An adenine molecule
• A ribose molecule
• Three phosphate molecules in a chain
• Third phosphate attached by high-energy bond
• When the bond is broken, energy is transferred
• When the bond is broken, ATP becomes ADP
• ADP becomes ATP through phosphorylation
• Phosphorylation requires energy release from cellular
respiration Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

P P P

Energy transferred Energy transferred


from cellular and utilized by
respiration used metabolic
to reattach reactions when
phosphate phosphate bond

P
P P
P
is broken 14
Release of Chemical Energy
• Chemical bonds are broken to release energy

• We burn glucose in a process called oxidation

15
4.5: Cellular Respiration
• Occurs in a series of reactions:
1. Glycolysis
2. “Prep” steps or intermediate steps
3. Citric acid cycle (aka TCA or Kreb’s Cycle)
4. Electron transport system

16
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

17
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

18
Glycolysis
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Phase 1 Glucose

Event 1 - Phosphorylation priming Carbon atom


P Phosphate

• Two phosphates added 2 ATP

2 ADP
to glucose
Fructose-1,6-diphosphate
• Requires ATP P P
Phase 2
cleavage

Dihydroxyacetone Glyceraldehyde

Event 2 – Splitting (cleavage) phosphate


P
phosphate
P

• 6-carbon glucose split into Phase 3


oxidation and P
2 NAD+
formation of
two 3-carbon molecules
4 ADP
ATP and release 2 NADH + H+
of high energy
4 ATP
electrons

2 Pyruvic acid

O2 O2 2 NADH + H+

2 NAD+

To citric acid cycle 2 Lactic acid


and electron transport
chain (aerobic pathway)

19
Glycolysis
Event 3 – Production of NADH and ATP Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
• Hydrogen atoms are released Phase 1 Glucose
Carbon atom
• Hydrogen atoms bind to NAD+ to priming
P Phosphate
2 ATP
produce NADH 2 ADP
• NADH delivers hydrogen atoms to
Fructose-1,6-diphosphate
electron transport system if oxygen Phase 2
P P

is available cleavage

• ADP is phosphorylated to become Dihydroxyacetone Glyceraldehyde


phosphate phosphate
ATP Phase 3
P P

• Two molecules of pyruvic acid are oxidation and


formation of
P
2 NAD+
4 ADP
ATP and release
produced of high energy
electrons
4 ATP
2 NADH + H+

• Two molecules of ATP are 2 Pyruvic acid

generated O2 O2 2 NADH + H+

2 NAD+

To citric acid cycle 2 Lactic acid


and electron transport
chain (aerobic pathway)

20
Anaerobic Reactions
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Phase 1 Glucose
• If oxygen is not priming Carbon atom
P Phosphate
2 ATP
available: 2 ADP

• Electron transport Fructose-1,6-diphosphate


P P

system cannot accept Phase 2


cleavage

new electrons from Dihydroxyacetone Glyceraldehyde

NADH
phosphate phosphate
P P
Phase 3
• Pyruvic acid is oxidation and
formation of
4 ADP
P
2 NAD+
ATP and release 2 NADH + H+

converted to lactic of high energy


electrons
4 ATP

acid 2 Pyruvic acid

O2 O2
• Glycolysis is 2 NADH + H+

2 NAD+

inhibited To citric acid cycle


and electron transport
2 Lactic acid

chain (aerobic pathway)

21
Aerobic Reactions
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• If oxygen is available: High energy


Glucose

electrons (e–) and


• Pyruvic acid is used to hydrogen ions (H+) 2 ATP

produce acetyl CoA


Pyruvic acid Pyruvic acid
• Citric acid cycle begins Cytosol

• Electron transport Mitochondrion


High energy

system functions electrons (e–) and


hydrogen ions (h+)

• Carbon dioxide and CO2

Acetyl CoA

water are formed


• 34 molecules of ATP Oxaloacetic
acid Citric acid

are produced per each High energy


electrons (e–) and
glucose molecule hydrogen ions (H+)

2 CO2

2 ATP

Electron transport chain

32-34 ATP
– +
O2 2e + 2H
H2O 22
Citric Acid Cycle
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• Begins when acetyl CoA Pyruvic acid from glycolysis

combines with oxaloacetic Cytosol


Carbon atom
P Phosphate

acid to produce citric acid CO2


NAD+

NADH + H+
Mitochondrion CoA Coenzyme A

• Citric acid is changed into CoA


Acetic acid

oxaloacetic acid through a Acetyl CoA

series of reactions (replenish molecule)

• Cycle repeats as long as


Oxaloacetic acid Citric acid

pyruvic acid and oxygen (finish molecule)


CoA
(start molecule)
NADH + H+
are available NAD+

Malic acid Isocitric acid

NAD+
Citric acid cycle CO2
• For each citric acid molecule: NADH + H+

Fumaric acid -Ketoglutaric acid


• One ATP is produced CO2
CoA
• Eight hydrogen atoms are FADH2 NAD+
FAD NADH + H+
transferred to NAD+ and FAD Succinic acid Succinyl-CoA

• Two CO2 produced ADP + P


CoA ATP

23
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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ATP synthase
ADP + P ATP
Energy
NADH + H+
Energy
2H+ + 2e–
FADH2 Energy
NAD+
2H+ + 2e–
FAD
Electron transport chain 2e–

2H+

O2
24
H2O
Summary of Cellular
Respiration Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Glucose

Glycolysis
High-energy electrons (e–)
1 sugar glucose is broken down in the Glycolysis 2 ATP

Cytosol
The 6-carbon
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
The 3-carbon pyruvic acids generated by glycolysis
enter the mitochondria.
2 Each loses a carbon
High-energy electrons (e–)
(generating CO2 and is combined with a coenzyme to CO2
form a 2-carbon acetyl coenzyme A (acetyl CoA). More
high-energy electrons are released.
Acetyl CoA

Each acetyl CoA combines with a 4-carbon oxaloacetic


3 the 6-carbon citric acid, for which the cycle
acid to form Citric acid
Oxaloacetic acid
is named. For each citric acid, a series of reactions
removes 2 carbons (generating 2 CO 2’s), synthesizes
1 ATP, and releases more high-energy electrons. Citric acid
Mitochondrion

The figure shows 2 ATP, resulting directly from 2 cycle


turns of the cycle per glucose molecule that enters High-energy electrons (e–)
glycolysis.
2 CO2

Electron Transport Chain 2 ATP


The high-energy electrons still contain most of the
chemical energy of the original glucose molecule. Electron
Special carrier
4
molecules bring the high-energy transport
32–34 ATP
electrons to a series of enzymes that convert much of chain
the remaining energy to more ATP molecules. The
2e– and 2H+
other products are heat and water. The function of
O2 H2 O
oxygen as the final electron acceptor in this last step is
why the overall process is called aerobic respiration. 25
Carbohydrate Storage
• Carbohydrate molecules from foods can enter:
• Catabolic pathways for energy production
• Anabolic pathways for storage

26
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 Anabolic
pathways pathways

27
Energy + CO2 + H2O Glycogen or Fat Amino acids
Summary of Catabolism of Proteins, Carbohydrates, and Fats

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Food

Proteins Carbohydrates
Carbohydrates Fats 1 Breakdown of large
macromolecules
(egg white) (toast,
(toast, hashbrowns)
hashbrowns) (butter) to simple molecules

Amino acids Simple sugars GlycerolFatty acids


(glucose)

Glycolysis ATP
Breakdown of simple
molecules
2 to acetyl
Pyruvic acid
coenzyme A
accompanied by
production of limited
ATP and high energy
Acetyl coenzyme
Acetyl coenzyme A
A electrons

Citric
CO2 3 oxidation
Complete
acid
cycle ATP
ATP of acetyl coenzyme A
High energy
High energy to H2O and CO2 produces
electrons
electrons carried
carried high energy electrons
by
by NADH
NADH and
and FADH
FADH22 (carried by NADH and
Electron
Electron FADH2), which yield much
transport ATP
transport ATP via the electron
chain
chain transport chain
2e– and 2H+
CO2
–NH2 ½ O H2O
2

28
Waste products

© Royalty Free/CORBIS.
4.6: Nucleic Acids and
Protein Synthesis
• Instruction of cells to synthesize proteins comes
from a nucleic acid, DNA

29
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

30
Structure of DNA
• Two polynucleotide Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

(a) Hydrogen
bonds P

chains – double-stranded
G C P

P
Thymine (T) Adenine (A) T
P

Cytosine (C) Guanine (G) P C G

• Hydrogen bonds hold


P

P
G C P

P
A P

G C

nitrogenous bases
A
Nucleotide strand

G C
T

together
C G

Segment A

of DNA
molecule

• Bases pair specifically


(A-T and C-G)
• Forms a helix
(b)

• DNA wrapped about Globular


Chromatin

histones forms
histone
proteins

chromatin
• chromosomes are
condensed chromatin (c)
Metaphase
chromosome
31
Animation:
DNA Structure

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32
DNA Replication
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A T

• Hydrogen bonds G
C

C
G

break between bases


C G
Original DNA
T A molecule

• Double strands C

C
G

unwind and pull apart T A

• New nucleotides pair C


A T

G
A

with exposed bases


T Region of
G C replication
C G
G
• Controlled by DNA T
A
T

polymerase A T A T

T A A
Newly formed
G C G C DNA molecules
T A T A

C G C G

C G G
C
T A A

33
Animation:
DNA Replication

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34
Genetic Code
• Specification of the correct sequence of amino
acids in a polypeptide chain
• Each amino acid is represented by a triplet code

35
RNA Molecules

• single-standed
• ribose
• uracil instead of thymine

36
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
37
RNA Molecules
• Messenger RNA (mRNA):
• Delivers genetic information
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from nucleus to the cytoplasm DNA RNA

S
P
• Single polynucleotide chain S
A U P

S
P

Direction of “reading” code


T A
• Formed beside a strand of S
P

DNA P
S
G C P
S

• RNA nucleotides are P


S
C G P
complementary to DNA S

nucleotides (exception – no P G C
S
P
thymine in RNA; replaced with S

uracil)
38
Animation:
Stages of Transcription

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39
Animation:
How Translation Works

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40
Protein Synthesis
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Cytoplasm 3 Translation begins as tRNA anticodons


DNA
recognize complementary mRNA codons, Amino acids
double
Nucleus thus bringing the correct amino acids into attached to tRNA
helix
position on the growing polypeptide chain
T A T A 6 tRNA molecules
G C G C 2 mRNA leaves can pick up another
A T A T Polypeptide
the nucleus chain molecule of the
Messenger and attaches same amino acid
GC DNA A T RNA to a ribosome and be reused
A T strands T U A
C G G G C
T A pulled G G C
apart G G C
C C G 5 At the end of the mRNA,
CG T U A the ribosome releases
T A C C G the new protein
G C C C G
A T G C G
C C G
A A T
GC A A T Nuclear 4 As the ribosome Amino acids
A T C C G pore moves along the represented
C G G G C
G G C 1 DNA mRNA, more amino A
T A acids are added Codon 1 Methionine
C C G information U
A A T is copied, or G
CG G G C
G G C transcribed, G
T A G Codon 2 Glycine
G C C C G into mRNA
A T T U A following C
C C G U
C C G complementary
C Codon 3 Serine
GC A A T base pairing
A T T U A C
C G G G C Messenger DNA G
T A A A T C Codon 4 Alanine
C C G RNA strand
G C A
G C
CG A
T A C G
C Codon 5 Threonine
G C A T G
Transcription G C Translation G
(in nucleus) G C (in cytoplasm) C Codon 6 Alanine
C G A
U A G
Codon 7 Glycine
C G G
C 41
Protein Synthesis
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1
2
1 3 Next amino acid
The transfer RNA molecule Growing 4
5 6
polypeptide
for the last amino acid added chain Transfer
holds the growing polypeptide Anticodon RNA
chain and is attached to its UGCCGU
AUGGGC U CCGCAA CGGCA GGC AAGC GU
complementary codon on mRNA.

1 2 3 4 5 6 7

Codons

1 Peptide bond
2
A second2 tRNA binds Growing 3
4 Next amino acid
polypeptide 5 6
complementarily to the chain Transfer
next codon, and in doing RNA
Anticodon
so brings the next amino UGCCGU
acid into position on the ribosome. AUGGGC U CCGCAA CGGCA GGC AAGC GU
A peptide bond forms, linking Messenger
the new amino acid to the 1 2 3 4 5 6 7 RNA
growing polypeptide chain.
Codons

The tRNA molecule that 1


2 3 Next
brought the
3 last amino
A acid 4
5 7 amino acid
to the ribosome is released 6
Transfer
to the cytoplasm, and will be RNA
CCG
used again. The ribosome UGC
CGU
moves to a new position at AUGGGC U CCGCAA CGGCA GGC AAGC GU
the next codon on mRNA. Messenger
1 2 3 4 5 6 7 RNA
Ribosome

1
2 3
4 4
A new tRNA complementary to 5 Next
6 7 amino acid
the next codon on mRNA brings
the next amino acid to be added Transfer
RNA
to the growing polypeptide chain. CGUCCG
AUGGGC U CCGCAA CGGCA GGC AAGC GU
Messenger
RNA

42
1 2 3 4 5 6 7
Animation:
Protein Synthesis

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43
Nature of Mutations
• Mutations – change in genetic
information Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

• Result when: Code for


glutamic
Mutation Code for
valine
• Extra bases are added acid

Direction of “reading” code


P T P T

or deleted S S

• Bases are changed P T P


A
S S

• May or may not change P C P C


S S
the protein (a) (b)

44
Protection Against Mutation

• Repair enzymes correct the mutations

45
Inborn Errors of Metabolism
• Occurs from inheriting a mutation that then
alters an enzyme
• This creates a block in an otherwise normal
biochemical pathway

46

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