1. Cellular Respiration

3. Figure 8.UN01Figure 8.UN01
Metabolic Pathways Often
Require Multiple Steps
Enzyme 1 Enzyme 2 Enzyme 3
Reaction 1 Reaction 2 Reaction 3
ProductStarting
molecule
A B C D

4. Figure 8.UN01Figure 8.UN01
Metabolic Pathways Often
Require Multiple Steps
Enzyme 1 Enzyme 2 Enzyme 3
Reaction 1 Reaction 2 Reaction 3
ProductStarting
molecule
A B C D
What happens when one of these steps goes awry?

5. Case Study: Why is Patrick
Paralyzed?
Maureen Knabb
Department of Biology
West Chester University

6. 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?

7. What could be responsible for Patrick’sWhat 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.

8. Which of the following processes requiresWhich of the following processes requires
energy?energy?
A: Creating ion gradients across membranes.
B: Muscle shortening.
C: Protein synthesis.
D: All of the above.

9. Figure 8.8aFigure 8.8a
(a) The structure of ATP
Adenosine Triphosphate (ATP) is the
Primary Energy Carrier in the Cell

10. 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

11. What would happen if Patrick lost his abilityWhat would happen if Patrick lost his ability
to make ATP?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

12. 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 3
ProductStarting
molecule
A B C D

13. 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 reaction
o Speed up chemical reactions

14. Course of
reaction
without
enzyme
EA
without
enzyme
EA with
enzyme
is lower
Course of
reaction
with enzyme
Reactants
Products
∆G is unaffected
by enzyme
Progress of the reaction
Freeenergy

15. Enzyme RegulationEnzyme Regulation
• Enzymes turn “on” and “off”
based on the needs of the cell
o 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 site
o Noncompetitive inhibition =
“other” site = allosteric site
• Feedback Inhibition

16. 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.

17. Consider the metabolic pathway below. If the enzyme responsible forConsider 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 D
B

18. DNA mutations can disruptDNA 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

19. * The Stages of Aerobic RespirationThe Stages of Aerobic Respiration

20. * The Stages of Aerobic RespirationThe Stages of Aerobic Respiration
Overall Reaction: C6H12O6 + 6O2 6 CO2 + 6H2O + ATP

21. 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.

22. • 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

23. • 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 Oxidation
Gaining Electrons is Reduction

24. NADNAD++
and NADHand NADH

25. * Figure 9.6-1Figure 9.6-1
Electrons
carried
via NADH
Glycolysis
Glucose Pyruvate
CYTOSOL MITOCHONDRION
ATP
Substrate-level
phosphorylation
Glycolysis Produces Pyruvate and NADH…

26. * Figure 9.6-2Figure 9.6-2
Electrons
carried
via NADH
Electrons carried
via NADH (and
FADH2)
Citric
acid
cycle
Pyruvate
oxidation
Acetyl CoA
Glycolysis
Glucose Pyruvate
CYTOSOL MITOCHONDRION
ATP ATP
Substrate-level
phosphorylation
Substrate-level
phosphorylation
The Pyruvate Feeds into the Citric Acid Cycle where…

27. * 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+
Citric
acid
cycle
+ 3 H+
…the Citric Acid Cycle Produces Even More NADH

28. * 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+
Citric
acid
cycle
+ 3 H+
…the Citric Acid Cycle Produces Even More NADH

29. Pyruvate
NAD+
NADH
+ H+
Acetyl CoA
CO2
CoA
CoA
CoA
2 CO2
ADP + P i
FADH2
FAD
ATP
3 NADH
3 NAD+
Citric
acid
cycle
+ 3 H+
…as well as some FADH2, some CO2 and more ATP
FADH2 is another
electron carrier
(similar to NADH)

30. Let’s review what we’ve done so far…
Glycolysis
1 Glucose (C6H12O6)
2 ATP + 2 NADH
2 Pyruvates (C3H3O3)
Energy Yield

31. 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…

32. * Figure 9.6-3Figure 9.6-3
Electrons
carried
via NADH
Electrons carried
via NADH and
FADH2
Citric
acid
cycle
Pyruvate
oxidation
Acetyl CoA
Glycolysis
Glucose Pyruvate
Oxidative
phosphorylation:
electron transport
and
chemiosmosis
CYTOSOL MITOCHONDRION
ATP ATP ATP
Substrate-level
phosphorylation
Substrate-level
phosphorylation
Oxidative
phosphorylation
The NADH and FADH2 Feed into the Electron Transport Chain…

33. * Figure 9.15Figure 9.15
Protein
complex
of electron
carriers
(carrying electrons
from food)
Electron transport chain
Oxidative phosphorylation
Chemiosmosis
I
II
III
IV
Q
Cyt c
FADFADH2
NADH ADP + P i
NAD+
H+
2 H+
+ 1
/2O2
H+
H+
H+
21
H+
H2O
ATP
The Electron Transport Chain
Coordinated Transport of High Energy Electrons is Coupled to
H+
Transport into the Inner Membrane Space
H+
H+
H+
H+
H+
H+
ATP
synthase

34. * Figure 9.15Figure 9.15
Protein
complex
of electron
carriers
(carrying electrons
from food)
Electron transport chain
Oxidative phosphorylation
Chemiosmosis
ATP
synthase
I
II
III
IV
Q
Cyt c
FADFADH2
NADH ADP + P i
NAD+
H+
2 H+
+ 1
/2O2
H+
H+
H+
21
H+
H2O
ATP
Chemiosmosis
Energy from H+
movement down the concentration gradient is
used to make ATP via ATP synthase
H+
H+
H+
H+
H+
H+
ATP

35. * Figure 9.15Figure 9.15
Protein
complex
of electron
carriers
(carrying electrons
from food)
Electron transport chain
Oxidative phosphorylation
Chemiosmosis
I
II
III
IV
Q
Cyt c
FADFADH2
NADH ADP + P i
NAD+
H+
2 H+
+ 1
/2O2
H+
H+
H+
21
H+
H2O
ATP
Chemiosmosis
Energy from H+
movement down the concentration gradient is
used to make ATP via ATP synthase
ATP
synthase
H+
H+
H+

36. 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

37. 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

38. 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

39. 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 ATP
Total: ~36 ATP

40. What Happens in the Absence of O2?

41. *Anaerobic RespirationAnaerobic Respiration
Glycolysis Only
•Make 2 ATP per glucose
(rather than 32-36 ATP)

42. *Anaerobic RespirationAnaerobic Respiration
Glycolysis Only
•Make 2 ATP per glucose
(rather than 32-36 ATP)
•In yeast, ethanol is
produced as a byproduct

43. *Anaerobic RespirationAnaerobic Respiration
Glycolysis 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

44. DNA mutations can disruptDNA 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

45. * Patrick suffered from lactate acidosisPatrick suffered from lactate acidosis
• Lactate (lactic acid) and pyruvate accumulated in his blood.
• Acidosis led to:
o Hyperventilation
o Muscle pain and weakness
o Abdominal pain and nausea

46. * 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).

47. * 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.