Transcript Chapter 9 - Slothnet

9
Pathways That Harvest
Chemical Energy
9 Pathways That Harvest Chemical Energy
9.1 How Does Glucose Oxidation Release
Chemical Energy?
9.2 What Are the Aerobic Pathways of
Glucose Metabolism?
9.3 How Does Oxidative Phosphorylation
Form ATP?
9.4 How Is Energy Harvested from Glucose
in the Absence of Oxygen?
9.5 How Are Metabolic Pathways Interrelated
and Regulated?
9 Pathways that Harvest Chemical Energy
Human infants are born with a lot of “brown
fat”—it has many mitochondria with ironcontaining pigments. When brown fat is
catabolized, its energy is released as heat,
which helps keep the baby warm.
Opening Question:
Can brown fat in adults be a target for
weight loss?
9.1 How Does Glucose Oxidation Release Chemical Energy?
Fuels: molecules whose stored energy
can be released for use.
In cells, energy from fuel molecules is
used to make ATP.
Glucose is the most common fuel in
cells.
9.1 How Does Glucose Oxidation Release Chemical Energy?
Cells get energy from glucose by
chemical oxidation in a series of
metabolic pathways.
Five principles of metabolic pathways:
• Complex transformations occur in a
series of separate reactions.
• Each reaction is catalyzed by a
specific enzyme.
9.1 How Does Glucose Oxidation Release Chemical Energy?
• Many metabolic pathways are similar
in all organisms.
• In eukaryotes, metabolic pathways
are compartmentalized in specific
organelles.
• Key enzymes in each pathway can be
inhibited or activated to alter the rate
of the pathway.
9.1 How Does Glucose Oxidation Release Chemical Energy?
Burning or metabolism of glucose:
C6H12O6 + 6 O2 →
6 CO2 + 6 H2O + free energy
An oxidation–reduction reaction:
glucose loses electrons (becomes
oxidized) and oxygen gains them
(becomes reduced).
9.1 How Does Glucose Oxidation Release Chemical Energy?
Glucose catabolism pathway stores the
free energy in ATP:
ADP + Pi + free energy → ATP
The ATP can be used to do cellular
work.
9.1 How Does Glucose Oxidation Release Chemical Energy?
ΔG (change in free energy) from
complete combustion of glucose is
–686 kcal/mol.
Highly exergonic; it drives the
endergonic formation of many ATP
molecules.
9.1 How Does Glucose Oxidation Release Chemical Energy?
Three catabolic processes harvest the
energy from glucose:
• Glycolysis: glucose is converted to
pyruvate; it is anaerobic.
• Cellular Respiration: pyruvate is
converted to three molecules of CO2;
it is aerobic.
9.1 How Does Glucose Oxidation Release Chemical Energy?
• Fermentation: converts pyruvate into
lactic acid or ethyl alcohol (anaerobic).
The breakdown of glucose is
incomplete and lactic acid and ethyl
alcohol still have a lot of energy.
Figure 9.1 Energy for Life
9.1 How Does Glucose Oxidation Release Chemical Energy?
Oxidation–Reduction (Redox)
reactions: one substance transfers
electrons to another substance.
Reduction: gain of one or more
electrons by an atom, ion, or
molecule.
Oxidation: loss of one or more
electrons.
9.1 How Does Glucose Oxidation Release Chemical Energy?
Oxidation and reduction always occur
together.
The compound that is reduced is the
oxidizing agent.
The compound that is oxidized is the
reducing agent.
In-Text Art, Ch. 9, p. 167 (1)
9.1 How Does Glucose Oxidation Release Chemical Energy?
In glucose metabolism, glucose is the
reducing agent, O2 is the oxidizing
agent.
Transfer of electrons is often
associated with the transfer of
hydrogen ions
H = H+ + e–
When a molecule loses H atoms it
becomes oxidized.
9.1 How Does Glucose Oxidation Release Chemical Energy?
The more reduced a molecule is, the
more energy it has.
In a redox reaction some energy is
transferred from the reducing agent
(glucose) to the reduced product.
Figure 9.2 Oxidation, Reduction, and Energy
9.1 How Does Glucose Oxidation Release Chemical Energy?
Coenzyme NAD+ is a key electron
carrier in redox reactions.
Figure 9.3 NAD+/NADH Is an Electron Carrier in Redox Reactions
9.1 How Does Glucose Oxidation Release Chemical Energy?
Oxygen accepts electrons from NADH:
NADH + H+ + ½ O2 → NAD+ + H2O
The reaction is exergonic:
ΔG = –52.4 kcal/mol
Oxidizing agent is molecular oxygen
(O2).
9.1 How Does Glucose Oxidation Release Chemical Energy?
Eukaryotic and prokaryotic cells
harvest energy from glucose using
different combinations of metabolic
pathways.
Some prokaryotes can harvest energy
by anaerobic respiration.
The five metabolic pathways occur in
different parts of the cell.
Figure 9.4 Energy-Yielding Metabolic Pathways
Table 9.1
9.2 What Are the Aerobic Pathways of Glucose Metabolism?
Glycolysis
• Takes place in the cytosol
• Converts glucose into 2 molecules of
pyruvate
• Produces 2 ATP and 2 NADH
• Occurs in 10 steps.
9.2 What Are the Aerobic Pathways of Glucose Metabolism?
Steps 1–5 require ATP (energyinvesting reactions).
Steps 6–10 yield NADH and ATP
(energy-harvesting reactions).
Figure 9.5 Glycolysis Converts Glucose into Pyruvate (Part 1)
Figure 9.5 Glycolysis Converts Glucose into Pyruvate (Part 2)
Figure 9.5 Glycolysis Converts Glucose into Pyruvate (Part 3)
9.2 What Are the Aerobic Pathways of Glucose Metabolism?
Steps 6 and 7 of glycolysis:
9.2 What Are the Aerobic Pathways of Glucose Metabolism?
Step 6 is an oxidation–reduction.
Exergonic; the energy is used to
reduce NAD+ to NADH.
Step 7 is substrate-level
phosphoryation.
Exergonic; the energy is used to
transfer a phosphate to ADP and form
ATP.
9.2 What Are the Aerobic Pathways of Glucose Metabolism?
Pyruvate Oxidation:
• Occurs in the mitochondrial matrix
• Produces acetate and CO2
• Acetate binds to coenzyme A to form
acetyl CoA
• Is a multistep reaction catalyzed by
the pyruvate dehydrogenase complex.
9.2 What Are the Aerobic Pathways of Glucose Metabolism?
Pyruvate oxidation:
Exergonic; one NAD+ is reduced to
NADH.
9.2 What Are the Aerobic Pathways of Glucose Metabolism?
Citric acid cycle
• Acetyl CoA is the starting point.
• The acetyl group is completely
oxidized to 2 molecules of CO2.
• Energy released is captured by ADP,
NAD+, FAD, and GDP.
Figure 9.6 The Citric Acid Cycle
9.2 What Are the Aerobic Pathways of Glucose Metabolism?
Step 8 of the citric acid cycle:
This oxidation reaction is exergonic.
9.2 What Are the Aerobic Pathways of Glucose Metabolism?
Overall, the oxidation of one glucose
molecule yields:
• Six CO2
• Ten NADH
• Two FADH2
• Four ATP
9.2 What Are the Aerobic Pathways of Glucose Metabolism?
Pyruvate oxidation and the citric acid
cycle are regulated by concentrations
of starting materials.
The starting molecules (acetyl CoA and
oxidized electron carriers) must be
replenished.
The electron carriers are reduced and
they must be reoxidized.
9.2 What Are the Aerobic Pathways of Glucose Metabolism?
If O2 is present, it accepts the electrons
and H2O is formed.
9.3 How Does Oxidative Phosphorylation Form ATP?
Oxidative phosphorylation: ATP is
synthesized by reoxidation of electron
carriers in the presence of O2.
Two stages:
• Electron transport
• Chemiosmosis
9.3 How Does Oxidative Phosphorylation Form ATP?
Electron transport:
• Electrons from NADH and FADH2
pass through the respiratory chain of
membrane-associated carriers.
• Electron flow results in a proton
concentration gradient across the
inner mitochondrial membrane.
9.3 How Does Oxidative Phosphorylation Form ATP?
Chemiosmosis:
• Electrons flow back across the
membrane through a channel protein,
ATP synthase, which couples the
diffusion with ATP synthesis.
9.3 How Does Oxidative Phosphorylation Form ATP?
Why does the electron transport chain
have so many steps?
Why not in one step?
2 NADH + 2 H+ + O2 → 2 NAD+ + 2 H2O
9.3 How Does Oxidative Phosphorylation Form ATP?
This reaction is extremely exergonic;
too much free energy would be
released all at once and could not be
harvested by the cell.
In a series of reactions, each releases
a small amount of energy that can be
captured by an endergonic reaction.
9.3 How Does Oxidative Phosphorylation Form ATP?
The respiratory chain is located in the
folded inner mitochondrial membrane.
Energy is released as electrons are
passed between carriers.
Figure 9.7 The Oxidation of NADH and FADH2 in the Respiratory Chain
9.3 How Does Oxidative Phosphorylation Form ATP?
Protons are also actively transported.
Protons accumulate in the
intermembrane space and create a
concentration gradient and charge
difference. This potential energy is
called the proton-motive force.
Diffusion of protons back across the
membrane is coupled to ATP
synthesis (chemiosmosis).
Figure 9.8 The Respiratory Chain and ATP Synthase Produce ATP by a Chemiosmotic Mechanism
(Part 1)
Figure 9.8 The Respiratory Chain and ATP Synthase Produce ATP by a Chemiosmotic Mechanism
(Part 2)
9.3 How Does Oxidative Phosphorylation Form ATP?
ATP synthesis is reversible.
ATP synthase can also act as an
ATPase, hydrolyzing ATP to ADP
and Pi.
ATP  ADP + Pi + free energy
Why is ATP synthesis favored?
9.3 How Does Oxidative Phosphorylation Form ATP?
• ATP leaves the mitochondrial matrix
as soon as it is made, keeping ATP
concentration in the matrix low, and
driving the reaction toward the left.
• The H+ gradient is maintained by
active transport.
9.3 How Does Oxidative Phosphorylation Form ATP?
The chemiosmosis hypothesis was a
departure from the conventional
scientific thinking of the time.
The first experimental evidence of
chemiosmosis came from studies on
chloroplast thylakoid membranes.
Figure 9.9 An Experiment Demonstrates the Chemiosmotic Mechanism (Part 1)
Figure 9.9 An Experiment Demonstrates the Chemiosmotic Mechanism (Part 2)
Working with Data 9.1: Experimental Demonstration of the
Chemiosmotic Mechanism
Experiments to demonstrate the
chemiosmosis hypothesis used
isolated chloroplast membranes with
embedded ATP synthase.
By moving the membranes from high to
low pH (high to low H+
concentrations), they were able to
drive ATP synthesis.
Working with Data 9.1: Experimental Demonstration of the
Chemiosmotic Mechanism
ATP formation was measured using:
• Luciferase, which catalyzes the
formation of a luminescent molecule if
ATP is present.
• Molybdate to measure
phosphorylation directly.
Working with Data 9.1, Table 1
Working with Data 9.1: Experimental Demonstration of the
Chemiosmotic Mechanism
Question 1:
Which two experiments show that a
proton gradient is necessary and
sufficient to stimulate ATP formation?
Explain your reasoning.
Working with Data 9.1: Experimental Demonstration of the
Chemiosmotic Mechanism
Question 2:
Why was there less ATP production in
the absence of Pi?
9.3 How Does Oxidative Phosphorylation Form ATP?
The structure and function of ATP
synthase is the same in all living
organisms.
It is a molecular motor with two parts:
• F0 unit—the transmembrane H+
channel
• F1 unit—projects into mitochondrial
matrix; rotates to expose active sites
for ATP synthesis
Figure 9.10 How ATP Is Made
9.3 How Does Oxidative Phosphorylation Form ATP?
These molecular motors can make up
to 100 ATP molecules per second.
The mechanism was demonstrated by
isolating the F1 unit and attaching
fluorescently labeled microfilaments to
it.
With no proton gradient, ATP was
hydrolyzed, causing the motor to spin
—easily visible in the spinning
microfilaments.
9.3 How Does Oxidative Phosphorylation Form ATP?
Although O2 is an excellent electron
acceptor, incomplete electron transfer
can result in toxic intermediates.
9.3 How Does Oxidative Phosphorylation Form ATP?
Superoxide and hydroxyl radicals have
unpaired electrons and react with
other molecules to gain or loose
electrons to become more stable.
This changes the structure and
function of the other molecules.
9.3 How Does Oxidative Phosphorylation Form ATP?
Superoxide damage has been
implicated in several human diseases
and aging.
Enzymes can “scavenge” the oxidizers
and convert them to water.
Antioxidant vitamins such as vitamin E
act in a similar way.
9.3 How Does Oxidative Phosphorylation Form ATP?
Many bacteria and archaea have
evolved pathways that allow them to
exist where O2 is scarce or absent, by
using other electron acceptors—
anaerobic respiration.
Table 9.2
9.4 How Is Energy Harvested from Glucose in the Absence
of Oxygen?
Without O2, some ATP can be
produced by glycolysis and
fermentation.
Fermentation occurs in the cytosol.
NAD+ is regenerated to keep
glycolysis going.
There are many types of fermentation;
the best understood are lactic acid
and alcohol fermentation.
9.4 How Is Energy Harvested from Glucose in the Absence
of Oxygen?
Lactic acid fermentation:
• Pyruvate is the electron acceptor
and lactate is the product.
• Occurs in microorganisms and some
muscle cells.
Figure 9.11 Fermentation (Part 1)
9.4 How Is Energy Harvested from Glucose in the Absence
of Oxygen?
During active exercise, O2 cannot be
delivered fast enough for aerobic
respiration.
Muscle cells then break down glycogen
and carry out lactic acid fermentation.
When lactate builds up, the increase in
H+ lowers pH and causes muscle
pain.
9.4 How Is Energy Harvested from Glucose in the Absence
of Oxygen?
Alcoholic fermentation:
• Yeasts and some plant cells
• Requires two enzymes to metabolize
pyruvate to ethanol
• Used to produce alcoholic
beverages
Figure 9.11 Fermentation (Part 2)
9.4 How Is Energy Harvested from Glucose in the Absence
of Oxygen?
Cellular respiration yields more energy
than fermentation.
• Glycolysis plus fermentation = 2 ATP
• Glycolysis plus cellular respiration =
32 ATP
Glucose is only partially oxidized in
fermentation, more energy remains in
the products than in CO2.
Figure 9.12 Cellular Respiration Yields More Energy Than Fermentation
9.4 How Is Energy Harvested from Glucose in the Absence
of Oxygen?
Two key events in the evolution of
multicellular organisms were the
increase in atmospheric O2 levels and
the development of metabolic
pathways to use that O2.
9.4 How Is Energy Harvested from Glucose in the Absence
of Oxygen?
In some eukaryotes, ATP must be used
to transport NADH into the
mitochondrial matrix.
NADH shuttle systems transfer
electrons captured by glycolysis onto
substrates that can move across
mitochondrial membranes.
9.5 How Are Metabolic Pathways Interrelated and Regulated?
Metabolic pathways do not operate in
isolation.
Many pathways share intermediate
molecules.
Pathways are regulated by enzyme
inhibitors.
Figure 9.13 Relationships among the Major Metabolic Pathways of the Cell
9.5 How Are Metabolic Pathways Interrelated and Regulated?
Catabolic interconversions:
Polysaccharides are hydrolyzed to
glucose, which enters glycolysis.
Lipids are broken down to
• glycerol → DHAP → glycolysis
• fatty acids → acetyl CoA → citric
acid cycle
9.5 How Are Metabolic Pathways Interrelated and Regulated?
Proteins are hydrolyzed to amino acids,
which feed into glycolysis or the citric
acid cycle.
9.5 How Are Metabolic Pathways Interrelated and Regulated?
Anabolic interconversions
Most catabolic reactions are reversible.
Gluconeogenesis: glucose formed
from citric acid cycle and glycolysis
intermediates.
Acetyl CoA can be used to form fatty
acids.
9.5 How Are Metabolic Pathways Interrelated and Regulated?
How do cells “decide” which pathways
to use?
Levels of substances in the metabolic
pool are quite constant.
Organisms regulate enzymes to
maintain balance between catabolism
and anabolism.
9.5 How Are Metabolic Pathways Interrelated and Regulated?
When jogging, energy is needed by leg
muscles and heart muscles.
Glucose is catabolized to provide
energy, and in the liver, more glucose
is made by anabolism from amino
acids and pyruvate.
How does the liver “know” that it should
be making glucose rather than
catabolizing it or storing it?
Figure 9.14 Interactions of Catabolism and Anabolism during Exercise
9.5 How Are Metabolic Pathways Interrelated and Regulated?
Systems biology seeks to understand
how biochemical pathways interact.
The pathways are regulated so that
levels of molecules such as blood
glucose remain constant.
Key enzymes are subject to allosteric
regulation.
9.5 How Are Metabolic Pathways Interrelated and Regulated?
Negative and positive feedback
A high concentration of a metabolic
product inhibits action of an enzyme in
the pathway.
Excess product of one pathway can
activate an enzyme in another
pathway, diverting raw materials away
from synthesis of the first product.
Figure 9.15 Regulation by Negative and Positive Feedback
Figure 9.16 Allosteric Regulation of Glycolysis and the Citric Acid Cycle (Part 1)
Figure 9.16 Allosteric Regulation of Glycolysis and the Citric Acid Cycle (Part 2)
9.5 How Are Metabolic Pathways Interrelated and Regulated?
The main control point in glycolysis is
phosphofructokinase (step 3), which is
inhibited by ATP.
In fermentation, phosphofructokinase
operates at a high rate to produce
ATP.
If O2 is present, more ATP is produced,
which inhibits the enzyme and slows
glycolysis.
9.5 How Are Metabolic Pathways Interrelated and Regulated?
The main control point in the citric acid
cycle is isocitrate dehydrogenase
(step 3).
It is inhibited by NADH and ATP; if too
much of either accumulates, the citric
acid cycle shuts down.
9.5 How Are Metabolic Pathways Interrelated and Regulated?
Acetyl CoA is another control point:
If ATP levels are high and the citric acid
cycle shuts down, accumulation of
citrate activates fatty acid synthesis
from acetyl CoA, diverting it to
storage.
Fatty acids may be metabolized later to
produce more acetyl CoA.
9 Answer to Opening Question
Brown fat cells make UCP1, a protein
that inserts in the mitochondrial inner
membrane and makes it permeable to
protons.
Thus the H+ concentration gradient is
not established, and ATP is not
synthesized. The energy released
during electron transport goes to heat
instead.
9 Answer to Opening Question
Adult humans have mostly white fat,
but researchers have bred mice that
make more UCP1 as adults.
These mice stay thinner than normal
mice because more of their food
energy goes to heat.
UCP1 may be useful in the fight against
obesity.