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Cellular Respiration
Figure 8.UN01Figure 8.UN01
Metabolic Pathways Often Require Multiple Steps
Enzyme 1 Enzyme 2 Enzyme 3
Reaction 1 Reaction 2 Reaction 3ProductStarting
molecule
A B C D
Figure 8.UN01Figure 8.UN01
Metabolic Pathways Often Require Multiple Steps
Enzyme 1 Enzyme 2 Enzyme 3
Reaction 1 Reaction 2 Reaction 3ProductStarting
molecule
A B C D
What happens when one of these steps goes awry?
Case Study: Why is Patrick Paralyzed?
Maureen Knabb
Department of Biology
West Chester University
Patrick at Ages 2 and 21Patrick at Ages 2 and 21
Patrick at 2: • When Patrick was 16 years old, his hand started twitching as he picked up a glass at dinner.
• Five months later (in February 2001), he fell down the steps at his home and was unable to climb the steps to the bus. He went to the ER for his progressive weakness.
• At Children’s Hospital of Philadelphia he was initially diagnosed with a demyelinating disease.
• He was treated with anti-inflammatory drugs and antibodies for 2 years with no improvement.
• What was wrong with Patrick?
By the time Patrick was 21 he was completely paralyzed
Why did Patrick lose his ability to move?
What could be responsible for Patrick’s What could be responsible for Patrick’s loss of mobility?loss of mobility?
A: His nervous system is not functioning properly.
B: His muscles are not functioning properly.
C: He cannot efficiently break down food for energy.
D: All of the above are possible causes.
Which of the following processes requires Which of the following processes requires energy?energy?
A: Creating ion gradients across membranes.
B: Muscle shortening.
C: Protein synthesis.
D: All of the above.
Figure 8.8aFigure 8.8a
(a) The structure of ATP
Adenosine Triphosphate (ATP) is the Primary Energy Carrier in the
Cell
3 Phosphate groups(triphosphate)
Adenine
Ribose(a) The structure of ATP
Figure 8.8a
Adenosine Triphosphate (ATP) is the Primary Energy Carrier in the
Cell
What would happen if Patrick lost his What would happen if Patrick lost his ability to make ATP?ability to make ATP?
A: His muscles would not be able to contract.
B: His neurons would not be able to conduct electrical signals.
C: Both A and B.
11
How is ATP generated?How is ATP generated?
• ATP is formed through metabolic pathways.
• In metabolic pathways, the product of one reaction is a reactant for the next.
• Each reaction is catalyzed by an enzyme.
12
Enzyme 1 Enzyme 2 Enzyme 3
Reaction 1 Reaction 2 Reaction 3ProductStarting
molecule
A B C D
What are enzymes?What are enzymes?• Enzymes (usually proteins)
are biological catalysts that are highly specific for their substrates (i.e., reactants).
• Enzymes are not consumed in the reaction.
• Enzymes lower the activation energy (the initial energy to start a reaction) of a reactiono Speed up chemical reactions
Course ofreactionwithoutenzyme
EA
withoutenzyme EA with
enzymeis lower
Course ofreactionwith enzyme
Reactants
Products
G is unaffectedby enzyme
Progress of the reaction
Free
ene
rgy
Enzyme RegulationEnzyme Regulation
• Enzymes turn “on” and “off” based on the needs of the cello Activators: Turn enzymes “ON”
• Positive allosteric regulation
o Inhibitors turn enzymes off• Irreversible = must make new
enzyme!• Reversible = inhibitor can “come
off”o Competitive inhibition =
active siteo Noncompetitive inhibition =
“other” site = allosteric site• Feedback Inhibition
CQ6: In competitive inhibition…CQ6: In competitive inhibition…
A: the inhibitor competes with the normal substrate for binding to the enzyme's active site.
B: an inhibitor permanently inactivates the enzyme by combining with one of its functional groups.
C: the inhibitor binds with the enzyme at a site other than the active site.
D: the competing molecule's shape does not resemble the shape of the substrate molecule.
Consider the metabolic pathway below. If the enzyme responsible for Consider the metabolic pathway below. If the enzyme responsible for converting A to C was mutated and nonfunctional, what would happen?converting A to C was mutated and nonfunctional, what would happen?
A: Levels of A would increase; levels of B, C, and D would decrease.
B: Levels of A and B would increase; levels of C and D would decrease.
C: Levels of A, B and C would increase; levels of D would decrease.
D: Levels of A, B, C, and D would all decrease.
A C DB
DNA mutations can disrupt DNA mutations can disrupt metabolic pathwaysmetabolic pathways
• Patrick suffered from a genetic disease that altered the structure of one protein.
• The protein was an enzyme.• The enzyme could potentially:
• lose its ability to catalyze a reaction.• lose its ability to be regulated.
• The enzyme that was mutated was involved in aerobic respiration
* The Stages of Aerobic RespirationThe Stages of Aerobic Respiration
* The Stages of Aerobic RespirationThe Stages of Aerobic Respiration
Overall Reaction: C6H12O6 + 6O2 6 CO2 + 6H2O + ATP
Overall yield = 2 ATP and 2 NADH + H+
Steps 1-3 Steps 4-6 Steps 7-10
ATP investment steps ATP producing steps
Occurs either with (aerobic) or without (anaerobic) oxygen.
• Glucose is not oxidized in a single step– It is broken down in a series of steps– Each step is catalyzed by an enzyme
• At key points, electrons are removed– Electrons travel with a proton (as a H atom)– H atoms are transferred to an electron carrier/acceptor, NAD+, via
a reduction-oxidation (redox) reaction• NAD+ is reduced* to NADH
VIP: Glycolysis Harvests Energy in a Stepwise Process
• Glucose is not oxidized in a single step– It is broken down in a series of steps– Each step is catalyzed by an enzyme
• At key points, electrons are removed– Electrons travel with a proton (as a H atom)– H atoms are transferred to an electron carrier/acceptor, NAD+, via
a reduction-oxidation (redox) reaction• NAD+ is reduced* to NADH
VIP: Glycolysis Harvests Energy in a Stepwise Process
*LEO goes GER: Losing Electrons is OxidationGaining Electrons is Reduction
NADNAD++ and NADH and NADH
* Figure 9.6-1Figure 9.6-1
Electronscarried
via NADH
Glycolysis
Glucose Pyruvate
CYTOSOL MITOCHONDRION
ATP
Substrate-levelphosphorylation
Glycolysis Produces Pyruvate and NADH…
* Figure 9.6-2Figure 9.6-2
Electronscarried
via NADH
Electrons carriedvia NADH (and
FADH2)
Citricacidcycle
Pyruvateoxidation
Acetyl CoA
Glycolysis
Glucose Pyruvate
CYTOSOL MITOCHONDRION
ATP ATP
Substrate-levelphosphorylation
Substrate-levelphosphorylation
The Pyruvate Feeds into the Citric Acid Cycle where…
* Figure 9.11Figure 9.11
Pyruvate
NAD
NADH+ H Acetyl CoA
CO2
CoA
CoA
CoA
2 CO2
ADP + P i
FADH2
FAD
ATP
3 NADH
3 NAD
Citricacidcycle
+ 3 H
…the Citric Acid Cycle Produces Even More NADH
* Figure 9.11Figure 9.11
Pyruvate
NAD
NADH+ H Acetyl CoA
CO2
CoA
CoA
CoA
2 CO2
ADP + P i
FADH2
FAD
ATP
3 NADH
3 NAD
Citricacidcycle
+ 3 H
…the Citric Acid Cycle Produces Even More NADH
Pyruvate
NAD
NADH+ H Acetyl CoA
CO2
CoA
CoA
CoA
2 CO2
ADP + P i
FADH2
FAD
ATP
3 NADH
3 NAD
Citricacidcycle
+ 3 H
…as well as some FADH2, some CO2 and more ATP
FADH2 is another electron carrier (similar to NADH)
Let’s review what we’ve done so far…
Glycolysis 1 Glucose (C6H12O6)
2 ATP + 2 NADH
2 Pyruvates (C3H3O3)
Energy Yield
Glycolysis
Citric Acid Cycle
1 Glucose (C6H12O6)2 ATP + 2 NADH
6 CO2 2 ATP + 8 NADH
+ 2 FADH2
2 Pyruvates (C3H3O3)
Energy Yield
Remember: C6H12O6 + 6O2 6 CO2 + 6H2O + ATP
Let’s review what we’ve done so far…
* Figure 9.6-3Figure 9.6-3
Electronscarried
via NADH
Electrons carriedvia NADH and
FADH2
Citricacidcycle
Pyruvateoxidation
Acetyl CoA
Glycolysis
Glucose Pyruvate
Oxidativephosphorylation:electron transport
andchemiosmosis
CYTOSOL MITOCHONDRION
ATP ATP ATP
Substrate-levelphosphorylation
Substrate-levelphosphorylation
Oxidative phosphorylation
The NADH and FADH2 Feed into the Electron Transport Chain…
* Figure 9.15Figure 9.15
Proteincomplexof electroncarriers
(carrying electronsfrom food)
Electron transport chainOxidative phosphorylation
Chemiosmosis
I
II
IIIIVQ
Cyt c
FADFADH2
NADH ADP P iNAD
H
2 H + 1/2O2
H
HH
21
H
H2O
ATP
The Electron Transport ChainCoordinated Transport of High Energy Electrons is Coupled to
H+ Transport into the Inner Membrane Space
H
HH
H
H
H
ATPsynthase
* Figure 9.15Figure 9.15
Proteincomplexof electroncarriers
(carrying electronsfrom food)
Electron transport chainOxidative phosphorylation
Chemiosmosis
ATPsynthase
I
II
IIIIVQ
Cyt c
FADFADH2
NADH ADP P iNAD
H
2 H + 1/2O2
H
HH
21
H
H2O
ATP
ChemiosmosisEnergy from H+ movement down the concentration gradient is
used to make ATP via ATP synthase
H
HH
H
H
H
ATP
* Figure 9.15Figure 9.15
Proteincomplexof electroncarriers
(carrying electronsfrom food)
Electron transport chainOxidative phosphorylation
Chemiosmosis
I
II
IIIIVQ
Cyt c
FADFADH2
NADH ADP P iNAD
H
2 H + 1/2O2
H
HH
21
H
H2O
ATP
ChemiosmosisEnergy from H+ movement down the concentration gradient is
used to make ATP via ATP synthase
ATPsynthase
H
HH
Glycolysis 1 Glucose (C6H12O6)
2 ATP + 2 NADH
6 CO2 2 ATP + 8 NADH
+ 2 FADH2
2 Pyruvates (C3H3O3)
Energy Yield
Let’s Take a Final Talley…
Citric Acid Cycle
Glycolysis 1 Glucose (C6H12O6)
6 CO2
2 Pyruvates (C3H3O3)
Energy Yield
Overall Reaction: C6H12O6 + 6O2 6 CO2 + 6H2O + ATP
Let’s Take a Final Talley…
2 ATP + 2 NADH
2 ATP + 8 NADH + 2 FADH2
10 NADH + 2 FADH2
Citric Acid Cycle
Oxidative Phosphorylation
Glycolysis
Citric Acid Cycle
1 Glucose (C6H12O6)
6 CO2
2 Pyruvates (C3H3O3)
Energy Yield
Overall Reaction: C6H12O6 + 6O2 6 CO2 + 6H2O + ATP
Let’s Take a Final Talley…
Oxidative Phosphorylation
2 ATP + 2 NADH
2 ATP + 8 NADH + 2 FADH2
6 O2
10 NADH + 2 FADH2
6 O2
6 H2O
ETC
H+ gradient
Glycolysis
Citric Acid Cycle
1 Glucose (C6H12O6)
6 CO2
2 Pyruvates (C3H3O3)
Energy Yield
Overall Reaction: C6H12O6 + 6O2 6 CO2 + 6H2O + ATP
Let’s Take a Final Talley…
Oxidative Phosphorylation
2 ATP + 2 NADH
2 ATP + 8 NADH + 2 FADH2
6 O2
10 NADH + 2 FADH2
6 O2
6 H2O
ETC
H+ gradient
~32 ATPTotal: ~36 ATP
What Happens in the Absence of O2?
*Anaerobic RespirationAnaerobic RespirationGlycolysis Only•Make 2 ATP per glucose (rather than 32-36 ATP)
*Anaerobic RespirationAnaerobic RespirationGlycolysis Only•Make 2 ATP per glucose (rather than 32-36 ATP)•In yeast, ethanol is produced as a byproduct
*Anaerobic RespirationAnaerobic RespirationGlycolysis Only•Make 2 ATP per glucose (rather than 32-36 ATP)•In yeast, ethanol is produced as a byproduct•In animals, lactate is produced as a byproduct
*DNA mutations can disrupt DNA mutations can disrupt
metabolic pathways metabolic pathways
*Patrick suffered from a genetic disease that altered the structure of one protein.
*The protein was an enzyme.*The enzyme could potentially:
*lose its ability to catalyze a reaction.*lose its ability to be regulated.
*The enzyme that was mutated was involved in aerobic respiration
* Patrick suffered from lactate acidosisPatrick suffered from lactate acidosis
• Lactate (lactic acid) and pyruvate accumulated in his blood.• Acidosis led to:
o Hyperventilationo Muscle pain and weaknesso Abdominal pain and nausea
* What happened to Patrick?What happened to Patrick?• He inherited a mutation
leading to a disease called pyruvate dehydrogenase complex disease (PDCD).
• Pyruvate dehydrogenase is an enzyme that converts pyruvate to acetyl CoA inside the mitochondria.
• The brain depends on glucose as a fuel. PDCD degenerates gray matter in the brain.
• Pyruvate accumulates, leading to lactate accumulation in the blood (lactate acidosis).
* Why did Patrick become paralyzed?Why did Patrick become paralyzed?A: He inherited a genetic disease that resulted in the
partial loss of an enzyme necessary for aerobic breakdown of glucose.
B: The enzyme that is necessary for metabolizing fats was defective.
C: He was unable to synthesize muscle proteins due to defective ribosomes.
D: He suffered from a severe ion imbalance due to a high salt diet.