Download Class22 2-9 Win17 Respiration Regulation and

Hans Krebs:
Citric acid, and opportunities lost and gained
Thursday February 9th, 2017
Class 22 Learning Goals
Respiration: Regulation and Fermentation
•  After this class, you should be able to:
•  Classify a microorganism as eukaryotic or prokaryotic based
on respiration details
•  Critically assess the usefulness of a particular regulation
mechanism or feedback loop for a respiring organism or cell
•  Describe several different respiration schemes that are not
aerobic respiration (and note environments in which these
schemes might be most favored)
•  Identify a fermentation reaction and compare the energetic
output with a similar aerobic reaction
Peer Instruction
Where are these found in the
fake cells shown here?
•  Electron Transport Chain
•  Krebs Cycle
•  Linking Step
•  Glycolysis
Fake Animal Cell
Fake Plant Cell
Peer Instruction
Diagram how the overall scheme of
respiration works in this prokaryote.
Include:
•  Electron Transport Chain
•  Krebs Cycle
•  Linking Step
•  Glycolysis
Clicker Question #1
The most efficient metabolism would make the
greatest number of ATP per glucose molecule.
Which type of cell has a more efficient metabolism?
Why?
1)  Eukaryotic --> it is bigger
2)  Prokaryotic --> it is smaller
3)  Eukaryotic --> more organelles to help with
complex reactions
4)  Prokaryotic --> no need to transport molecules
through organelle membranes
5)  They are equally efficient
Peer Instruction
Why is this negative feedback loop a good idea for the cell?
How can the product molecule regulate an enzyme?
Why are positive feedback loops rare in biology?
Clicker Question #2
Examples of positive feedback are relatively
rare in biological regulation. Why is this?
1)  Positive feedback does not equilibrate response to a
particular appropriate cellular level
2)  Positive feedback requires more regulatory molecules
3)  Positive feedback is not possible in cellular
environments
4)  Positive feedback can quickly become costly
Explain how “feedback
inhibition” works with this enzyme.
Peer Instruction
When ATP binds here,
the reaction rate slows
dramatically
Fructose-1,6-
bisphosphate
at active site
(as the reaction is
completed)
ADP at
active site
Peer Instruction
This step
is regulated
by ATP
These steps are
also regulated via
feedback inhibition,
by ATP and NADH
Citrate
Acetyl CoA
Oxaloacetate
Does it make sense for the cell to use feedback inhibition here?
Peer Instruction
Why can a mutation that allows an additional input pathway
improve the relative fitness of an organism?
Peer Instruction
Pathway for synthesis
of RNA, DNA
Fats
Phospholipids
Fatty acids
Glycogen
or starch
Glucose
Pyruvate
Acetyl CoA
GLYCOLYSIS
KREBS
CYCLE
Lactate
(from fermentation)
How does diversification of metabolic output
improve fitness for an organism?
Several intermediates
used as substrates in
amino acid synthesis
Metabolism: Full complexity
Peer Instruction
‘Anaerobic’ means ‘without oxygen’.
What do anaerobic respirators do differently in metabolism?
Are C-C and C-H the only bonds that contain energy?
What molecules are broken down by chemolithotrophs?
Is ATP synthase the only ATP source in human respiration?
Fermentation pathway:
Fermentation
by-product
Peer Instruction
Intermediate accepts
electrons from NADH
Explain how fermentation works.
How does the ATP yield of fermentation compared to
that of aerobic respiration?
In what conditions would the evolution of enzymes and
regulation to allow fermentation be advantageous?
Peer Instruction
Fermentation pathways:
Allowing cells to make ATP and regenerate NAD+ without oxygen
Fermentation
by-product
Intermediate accepts
electrons from NADH
Lactic acid fermentation occurs in humans.
No intermediate;
pyruvate accepts
electrons from NADH
2 Pyruvate
2 Lactate
Peer Instruction
Fermentation pathways:
Allowing cells to make ATP and regenerate NAD+ without oxygen
Fermentation
by-product
Intermediate accepts
electrons from NADH
Alcohol fermentation occurs in yeast.
2 Ethanol
2 Pyruvate
Concept Questions
• 
Is this most likely prokaryotic or eukaryotic? How do you know?
–  A cell that is more basic than its environment
–  A cell that spends extra ATP to build membrane channels
–  A cell that concentrates ATP synthase in compartments of membrane
• 
Which of these regulation methods would be most useful? Why?
–  Glucose makes 3 of the glycolysis enzymes work more slowly
–  ATP slows the linking step
–  Complex II prevents the formation of more mitochondria
• 
What respiration scheme might work better than aerobic:
–  In a peat bog?
–  In outer space?
–  In the midst of a coral reef?
• 
Imagine a species that metabolizes fructose down to methanol, and then feeds that
methanol into their version of the Krebs’ cycle. Draw a reaction that would allow
fermentation in this species. You can use the given diagrams for ethanol fermantation
as a guide.
–  What does this species produce as a final product? How does it smell?
–  Does this species make a lot of ATP compared to its own aerobic pathway?
•  Metabolism: In Review
Key Concepts
–  Glycolysis: Glucose is processed to pyruvate through the
glycolysis reactions in the cytoplasm
–  Linking Step: Pyruvate is transferred into the mitochondria and
transformed into the ‘sticky’ 2-carbon Acetyl-CoA
–  Krebs Cycle: Acetyl-CoA feeds the Krebs cycle, which uses
the oxidation of carbohydrates to form reducing power (as
NADH, FADH2)
–  Electron Transport Chain: High-energy electrons are driven
through membrane proteins that pump protons to produce a
gradient, with oxygen acting as the final electron acceptor in
most organisms
–  Oxidative Phosphorylation: ATP synthase uses gradient
energy to catalyze the formation of the energy currency of the
cell, ATP
–  Regulation
• 
• 
• 
• 
• 
Fermentation
Alternative pathways
Non-aerobic respiration mechanisms
Differences in prokaryotes and eukaryotes
Enzyme feedback inhibition
Clicker Question #3
Carbon dioxide cannot be removed from the mitochondria,
which process is likely to shut down first?
1. 
2. 
3. 
4. 
Glycolysis
the Linking Step
the Electron Transport Chain
the Krebs Cycle
Clicker Question #4
You are a single-celled organism with a full set of respiration
enzymes and essential precursor molecules.
You are given your choice: You can have 20 of one of the
following molecules….which would you rather have to
maximize your ATP production?
1.  NADH
2.  A proton (moved from your cytoplasm
outside your cell)
3.  GTP
4.  Acetyl-CoA
5.  FAD+
6.  There are two equal best options
Clicker Question #5
Prokaryote v. Eukaryote:
NADH is an extremely large and polar molecule. Each
NADH is worth roughly 2.4 ATP.
In eukaryotes, several NADH molecules are made in the
cytoplasm, but the electron transport chain is
processed in the mitochondria. The mitochondria
typically has a high concentration of NADH.
So what?
1)  This will lower the yield of ATP per glucose in
prokaryotes
2)  This will raise the yield of ATP per glucose in
eukaryotes
3)  Both eukaryotes and prokaryotes will make the
same amount of ATP per glucose
Clicker Question #6
You want to genetically engineer a prokaryote to have a stronger
metabolism (in other words, to produce more ATP per glucose).
There are many parts of the system that you could try to reengineer.
Which one, if successful, might give you the best impact?
1. 
2. 
3. 
4. 
5. 
Create a ‘trapping step’ enzyme that does not cost 1 ATP
Allow Complex II to pump a proton across the lipid membrane in the
ETC
Change ATP synthase to produce twice as many ATP with the same
gradient
Alter Krebs cycle intermediates to produce ATP instead of GTP
Make the linking step work more efficiently