1. Evaluating the Quick Fix: Weight Loss Drugs and Cellular Respiration
Pamela L. Freeman, Jennifer A. Maki, Kara R. Thoemke, Monica H. Lamm, and Clark R. Coffman

2. Objectives
Explain how the energy from sugars is transformed into ATP via cellular respiration.
Predict an outcome if there is a perturbation in a cellular pathway.
State and evaluate a hypothesis.
Interpret data from a graph, and use that data to make inferences about the action of a drug.
Please sit with your group,
have your clicker ready,
have your homework in hand, and
pack your phone and computer away

3. [Prompt your students that today they will:
Work in groups to apply their knowledge of cellular respiration.
Interpret data from primary literature.
Evaluate and make a decision about the safety of a weight loss drug.
and that it is expected they might feel challenged by the activities.]
Delete this slide before presentation in class or adjust as fits instructor need.

4. Cellular Respiration Mitochondria Acetyl CoA Pyruvate NADH Glycolysis
Glucose
Glycolysis
GTP
CO2
NADH
ATP
Mitochondria
Citric acid cycle
Cellular Respiration
Show the diagram and ask if there are any questions from the homework. Alternatively, prepare a clicker question or two and spot check their cellular respiration knowledge.
Briefly introduce the activity and ask students to read through the introduction material and complete Question 1 individually. Display this slide or the slide with Figure 1 while students are working.
Mitochondrial Electron Transport Chain figure: The original uploader was Rozzychan at English Wikipedia - Transferred from en.wikipedia to Creative Commons by Vojtech.dostal.
Image adapted from:

5. Display while discussing answers to question 1.
Figure 1. Mean (+SE) glucose oxidation (pmol/min/mg) in myotubule cell cultures grown without drug (control) or in the presence of 2,4-dinitrophenol (DNP) (p < 0.01; n = 8 replicates).
Data adapted from: Gaster, M Biochimica et Biophysica Acta. 1772:

6. [Other areas of discussion for Figure 1:
Q1. Determine and summarize what happens to glucose oxidation rate with DNP.
[Other areas of discussion for Figure 1:
What other information can be gleaned from the figure and caption?
Explain the meaning of:
rate
P-value
standard error]
Q2. Draw in your predicted concentration of ATP for question 2 and explain your answer.
Delete the bracketed material before presentation in class or shape to fit your discussion.

7. Display while students individually answer question 2, drawing their prediction on the graph.
Figure 1. Mean (+SE) glucose oxidation (pmol/min/mg) in myotubule cell cultures grown without drug (control) or in the presence of 2,4-dinitrophenol (DNP) (p < 0.01; n = 8 replicates).
Figure 2. Mean (+SE) ATP levels (normalized to control) in myotubule cell cultures grown without drug (control) or in the presence of 2,4-dinitrophenol (DNP) (n = 3 replicates)
Data adapted from: Gaster, M Biochimica et Biophysica Acta. 1772:

8. Q2. What did you predict would happen to the ATP levels in the cells exposed to DNP?
Stay the same
Increase
Decrease

9. Animated slide – movements will be visible only during slide show; view before editing
Display while discussing answers to question 2.
Follow-up questions to Q1 and 2.
Describe the difference in magnitude.
How can you tell if the difference is significant?
The red line is present to help students discriminate between standard error measurements. While not an exact measure of significance, the lack of overlap in the standard errors indicates what the general trend may be. The p-value is the real indicator of significance.
Ask students to generate hypotheses to explain the results (Q3 on worksheet).
Data Adapted from: Gaster, M Insulin resistance and the mitochondrial link. Lessons from cultured human myotubes. Biochimica et Biophysica Acta. 1772:
Figure 2. Mean (+SE) ATP levels (normalized to control) in myotubule cell cultures grown without drug (control) or in the presence of 2,4-dinitrophenol (DNP) (p< 0.05; n = 3 replicates)
Figure 1. Mean (+SE) glucose oxidation (pmol/min/mg) in myotubule cell cultures grown without drug (control) or in the presence of 2,4-dinitrophenol (DNP) (p < 0.01; n = 8 replicates).
Data Adapted from: Gaster, M Biochimica et Biophysica Acta. 1772:

10. Q3. What hypotheses explain the results in Figure 2?
[List here or on the board all the different hypotheses generated by students.]

11. In which area of the mitochondria will the pH be higher?
[Before discussion of the mechanism of DNP, ask a question to make sure students are thinking.]
In which area of the mitochondria will the pH be higher?
Intermembrane space
Matrix
[Insert a textbook image of a mitochondrion with the electron transport chain, protons being pumped, etc.]
Delete the bracketed material before presentation in class and add a cross sectional image of a mitochondria.

12. How does DNP work? - - H+ H+
Animated slide – movements will be visible only during slide show; view before editing
Please see article for explanation of DNP mechanism.
Delete the bracketed material before presentation in class.
Mitochondrial Electron Transport Chain figure: The original uploader was Rozzychan at English Wikipedia - Transferred from en.wikipedia to Creative Commons by Vojtech.dostal.
[Use this slide to explain the mechanism of DNP. Alternatively, build a similar slide using the next side and images from your textbook.]

13. How does DNP work?
[Insert a textbook image of a mitochondrion with the electron transport chain, protons being pumped, etc.
Use this slide to explain the mechanism of DNP. The mitochondrion image should be positioned so that the custom animation results in the movement of the DNP molecules into the matrix.]
Animated slide – movements will be visible only during slide show; view before editing
Please see article for explanation of DNP mechanism. H+ - - H+

14. Q4. Given this data and what you’ve learned, what advice would you give Miguel?
Take the DNP
Don’t take the DNP

15. Q5. Where does the weight go when someone loses weight?

17. Cellular Respiration
This figure is the basis for the homework assignment.
Mitochondrial Electron Transport Chain figure: The original uploader was Rozzychan at English Wikipedia - Transferred from en.wikipedia to Creative Commons by Vojtech.dostal.
Image adapted from: