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Chapter 4 Cellular Metabolism
ATP: Energy for Cells
• ATP (adenosine triphosphate) is the energy
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currency of cells.
ATP is constantly regenerated from ADP
(adenosine diphosphate) after energy is expended
by the cell.
Use of ATP by the cell has advantages:
1) can be used in many types of reactions.
2) When ATP → ADP + P, energy released is
sufficient for cellular needs, little energy is wasted.
• ATP is called a “high-energy” compound
because a phosphate group is easily
removed.
ATP’s structure
ATP is a nucleotide made of adenine and ribose and
three phosphate groups.
The ATP cycle
Function of ATP
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Cells make use of ATP for:
Chemical work
–to synthesize macromolecules
Transport work
–needed to pump substances across the plasma
membrane (Active Transport)
Mechanical work
–for cellular movements
Two types of metabolic reactions
Anabolism
• larger molecules
are made
•synthesis
• requires energy
Catabolism
• larger molecules are
broken down
•decomposition
• releases energy –
why?
4-2
Anabolism
Why is it needed?
for cellular growth and repair
Dehydration synthesis
• type of anabolic process
• used to make polysaccharides, triglycerides, and
proteins
• produces water
4-3
Anabolism
4-4
Catabolism
breaks down larger molecules into smaller ones
Hydrolysis
• a catabolic process
• used to decompose carbohydrates, lipids, and proteins
• water is used
• reverse of dehydration synthesis
4-5
Catabolism
4-6
Review anabolism and
catabolism
http://www.youtube.com/watch?
v=yiuRXnyxcEA&feature=relate
d
Review ATP
http://www.youtube.com/watch?
v=AhuqXwvFv2E
Enzymes
• Enzymes – biological catalysts, speed up
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reactions without themselves being
changed
Are specific – work on certain substrates
Written above the reaction arrow
Promotes effective collisions
Does not change the overall heat of
reaction
Lowers the activation energy
Energy of activation (Ea)
• Active site
• – area on enzyme where substrate fits
• The active site may undergo a slight change
in shape, called induced fit, in order to
accommodate the substrate(s).
• The enzyme and substrate form an enzymesubstrate complex during the reaction.
• The enzyme is not changed by the reaction,
and it is free to act again.
Induced fit model
Control of Metabolic
Reactions
Review - Enzymes
• control rates of metabolic reactions
• lower activation energy needed to start reactions
• globular proteins with specific shapes
• not consumed in chemical reactions
• substrate specific
• shape of active site determines substrate
4-7
Control of Metabolic
Reactions
Metabolic pathways - review
• series of enzyme-controlled reactions leading to formation of a
product
• each new substrate is the product of the previous reaction
Enzyme names commonly
• reflect the substrate
• have the suffix – ase
• sucrase, lactase, protease, lipase
4-8
Enzymatic reaction
Control of Metabolic
Reactions
Cofactors
• make some enzymes
active
• ions or coenzymes
Factors that affect or alter enzymes
• temperature
• radiation
• electricity
• chemicals
• changes in pH
•Will cause denaturing
Coenzymes
• organic molecules
that act as cofactors
• vitamins
4-9
Factors Affecting Enzymatic
Speed
• Enzymatic reactions proceed with great
speed provided there is enough substrate
to fill active sites most of the time.
• Enzyme activity increases as substrate
concentration increases because there are
more collisions between substrate
molecules and the enzyme.
Temperature and pH
• As the temperature rises, enzyme activity
increases because more collisions occur
between enzyme and substrate.
• If the temperature is too high, enzyme
activity levels out and then declines rapidly
because the enzyme is denatured.
• Each enzyme has an optimal pH at which
the rate of reaction is highest.
Rate of an enzymatic reaction as
a function of temperature and pH
Enzyme Review
http://lpscience.fatcow.com/jwanamaker/
animations.htm
• http://highered.mcgrawhill.com/sites/0070960526/student_view0/c
hapter6/animations.html
Cellular Respiration
• The overall equation for cellular
respiration is opposite that of
photosynthesis:
• C6H12O6 + 6O2 → 6CO2 + 6H2O +
Energy
• In this reaction, glucose is oxidized and
oxygen is reduced to become water.
• The complete oxidation of a mol of
glucose releases 686 kcal of energy that
is used to synthesize ATP.
• Each reaction requires a specific enzyme.
• Substrate concentration, temperature, pH, and
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enzyme concentration affect the rates of
reactions.
Most metabolic pathways are regulated by
feedback inhibition.
Cellular respiration involves oxidation-reduction
reactions and accounts for the flow of energy
through all living things.
Cellular Respiration
Occurs in three series of reactions
1. Glycolysis
2. Citric acid cycle
3. Electron transport chain
Produces
• carbon dioxide
• water
• ATP (chemical energy)
• heat
Includes
• anaerobic reactions (without O2) - produce little ATP
• aerobic reactions (requires O2) - produce most ATP
4-11
Overview of Cellular Respiration
• General purpose??
• The oxidation of glucose is an exergonic
reaction (releases energy) which drives ATP
synthesis, which is an endergonic reaction
(energy is required).
• The overall equation for cellular respiration
shows the coupling of glucose breakdown to
ATP buildup.
• The breakdown of one glucose molecule
results in a maximum of 36 to 38 ATP
molecules, representing about 40% of the
potential energy within the glucose molecule.
ATP Molecules - review
• 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 released from cellular respiration
4-12
Cellular respiration
Phases of Complete Glucose
Breakdown
• Glycolysis – the breakdown of glucose to
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two molecules of pyruvate (pyruvic acid) in
the cytoplasm with no oxygen needed;
yields 2 ATP
Really – 2 ATP  4 ATP (net 2)
Occurs without oxygen (anaerobic)
In cytoplasm – mitochondria not needed
Also called fermentation – lactic acid
fermentation in us
• Now – enter the mitochondria:
• Citric acid cycle – a cyclical series of oxidation
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reactions that give off CO2 and produce one ATP
per cycle; occurs twice per glucose molecule
Electron transport system – a series of carriers that
accept electrons removed from glucose and pass
them from one carrier to the next until the final
receptor, O2 is reached; water is produced; energy
is released and used to synthesize 32 to 34 ATP on
its own
To review:
1. Glycolysis – in cytosol
(anaerobic)
2. Citric Acid Cycle (Kreb’s
Cycle) – in mitochondria (aerobic)
3. Electron Transport Chain – in
mitochondria (aerobic)
Outside the Mitochondria:
Glycolysis
• Glycolysis occurs in the cytoplasm and is
the breakdown of glucose to two pyruvate
molecules.
• Glycolysis is universally found in all
organisms and likely evolved before the
citric acid cycle and electron transport
system.
• Glycolysis does not require oxygen.
Glycolysis
• series of ten reactions
• breaks down glucose into 2 pyruvic acids
• occurs in cytosol
• anaerobic phase of cellular respiration
• yields two ATP molecules per glucose
Summarized by three main events
1. phosphorylation
2. splitting
3. production of NADH (high-energy fuel molecule) and
ATP
4-13
Glycolysis
The resulting 2 pyruvates convert into Acetyl CoA to ready for the aerobic phases.
Glycolysis
Event 1 - Phosphorylation
• two phosphates
added to glucose
• requires ATP
Event 2 – Splitting (cleavage)
• 6-carbon glucose split
into two 3-carbon
molecules
4-14
Glycolysis Summary
• Inputs:
• Glucose
• 2 NAD+
• 2 ATP
• 4 ADP + 2 P
• Outputs:
• 2 pyruvate
• 2 NADH
• 2 ADP
• 2 ATP (net gain)
Anaerobic Reactions
If oxygen is not available • electron transport
chain cannot accept
NADH
• pyruvic acid is
converted to lactic acid
• glycolysis is inhibited
• ATP production
declines
4-16
Aerobic Reactions
If oxygen is available –
• pyruvic acid is used
to produce acetyl CoA
• citric acid cycle
begins
• electron transport
chain functions
• carbon dioxide and
water are formed
• 36 molecules of ATP
produced per glucose
molecule
4-17
Inside the Mitochondria
• A mitochondrion is a cellular organelle that has a double
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membrane, with an intermembrane space between the
two layers.
Cristae are folds of inner membrane that jut out into the
matrix, the innermost compartment, which is filled with a
gel-like fluid.
The transition reaction and citic acid cycle occur in the
matrix; the electron transport system is located in the
cristae.
Transition Reaction
• The transition reaction connects glycolysis to the
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citric acid cycle, and is thus the transition
between these two pathways.
Pyruvate is converted to a C2 acetyl group
attached to coenzyme A (CoA), and CO2 is
released.
During this oxidation reaction, NAD+ is converted
to NADH + H+; the transition reaction occurs
twice per glucose molecule.
Citric Acid Cycle
• The citric acid cycle is a cyclical metabolic
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pathway located in the matrix of the
mitochondria.
Each acetyl group received from the transition
reaction is oxidized to 2 CO2 molecules.
• During the cycle, oxidation occurs when NAD+
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accepts electrons in three sites and FAD accepts
electrons once.
Substrate-level phosphorylation results in a gain of
one ATP per every turn of the cycle; it turns twice per
glucose.
During the citric acid cycle, the six carbon atoms in
glucose become CO2.
The transition reaction produces two CO2, and the
citric acid cycle produces four CO2 per molecule of
glucose.
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
• for each citric acid
molecule:
• one ATP is produced
• eight hydrogen atoms
are transferred to NAD+
and FAD
• two CO2 produced
4-18
Citric acid cycle
Citric acid cycle inputs and
outputs per glucose molecule
• Inputs:
• 2 Acetyl-Co-A
• 6 NAD+
• 2 FAD
• 2 ADP + 2 P
• Outputs:
• 4 CO2
• 6 NADH
• 2 FADH2
• 2 ATP
ATP check!!!
• From glycolysis –
• 2 ATP
• From citric acid cycle
• 2 ATP
Electron Transport System
• The electron transport system located in the
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cristae of mitochondria is a series of protein
carriers, that pass electrons from one to the
other.
Electrons carried by NADH and FADH2 enter the
electron transport system.
As a pair of electrons is passed from carrier to
carrier, energy is released and is used to form
ATP molecules by oxidative phosphorylation.
• Oxygen receives energy-spent electrons at
the end of the electron transport system.
• Next, oxygen combines with hydrogen, and
water forms:
• ½ O2 + 2 e- + 2 H+ → H2O
• When NADH carries electrons to the first
carrier, enough energy is released by the
time electrons are accepted by O2 to produce
three ATP; two ATP are produced when
FADH2 delivers electrons to the carriers.
Overview of the electron
transport system
Electron Transport Chain
• NADH and FADH2 carry electrons to the ETC
• ETC 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
4-19
Energy Yield from Glucose
Metabolism – new check!!
• Per glucose molecule, there is a net gain
of two ATP from glycolysis, which occurs in
the cytoplasm by substrate-level
phosphorylation.
• The citric acid cycle, occurring in the matrix
of mitochondria, adds two more ATP, also
by substrate-level phosphorylation.
• Most ATP is produced by the electron
transport system.
• Per glucose molecule, ten NADH and two
FADH2 take electrons to the electron transport
system; three ATP are formed per NADH and
two ATP per FADH2.
• Electrons carried by NADH produced during
glycolysis are shuttled to the electron transport
chain by an organic molecule.
Accounting of energy yield per
glucose molecule breakdown
Summary of Cellular
Respiration
4-20
Review link
http://www.sumanasinc.com/we
bcontent/animations/content/cell
ularrespiration.html
Summary of Catabolism of Proteins,
Carbohydrates, and Fats
4-21
**Transparency
STOP
Carbohydrate Storage
Excess glucose stored as
• glycogen (primarily by liver and muscle cells)
• fat
• converted to amino acids
4-22
Sickle-cell disease in humans
Cause and Repair of Mutations
• Mutations can be spontaneous or caused by
environmental influences called mutagens.
• Mutagens include radiation (X-rays, UV
radiation), and organic chemicals (in
cigarette smoke and pesticides).
• DNA polymerase proof reads the new strand
against the old strand and detects
mismatched pairs, reducing mistakes to one
in a billion nucleotide pairs replicated.
Transposons: Jumping Genes
• Transposons are specific DNA sequences
that move from place to place within and
between chromosomes.
• These so-called jumping genes can cause
a mutation to occur by altering gene
expression.
• It is likely all organisms, including humans,
have transposons.
Cancer: A Failure of Genetic
Control
• Cancer is a genetic disorder resulting in a tumor,
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an abnormal mass of cells.
Carcinogenesis, the development of cancer, is a
gradual process.
Cancer cells lack differentiation, form tumors,
undergo angiogenesis and metastasize.
Cancer cells fail to undergo apoptosis, or
programmed cell death.
Structure of DNA
• 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
4-25
RNA Molecules
Messenger RNA (mRNA) • delivers genetic information
from nucleus to the cytoplasm
• single polynucleotide chain
• formed beside a strand of DNA
• RNA nucleotides are
complementary to DNA
nucleotides (exception – no
thymine in RNA; replaced with
uracil)
• making of mRNA is
transcription
4-26
RNA Molecules
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
4-27
Protein Synthesis
4-28
Protein Synthesis
4-29
DNA Replication
• hydrogen bonds break
between bases
• double strands unwind
and pull apart
• new nucleotides pair
with exposed bases
• controlled by DNA
polymerase
4-30
Mutations
Mutations – change in genetic
information
Result when
• extra bases are added or
deleted
• bases are changed
May or may not change the
protein
Repair enzymes correct
mutations
4-31
Clinical Application
Phenylketonuria
PKU
• enzyme that breaks down the amino acid phenylalanine
is missing
• build up of phenylalanine causes mental retardation
• treated by diets very low in phenylalanine
4-32