Case Study Section 3 – Ox. Phos. Based on “Wrestling with Weight Loss: The Dange
ID: 89786 • Letter: C
Question
Case Study Section 3 – Ox. Phos.
Based on “Wrestling with Weight Loss: The Dangers of a Weight-Loss Drug” by Susan M. DeSimone and Annie Prud’homme-Genereux and “A Diet to Die For: An Exploration of Oxidative Phosphorylation” by Terry Platt and Eric Ribbens (National Center for Case Study Teaching in Science)
The Situation:
A good friend of yours, Connor Sick, is a member of the WVU wrestling team but has been struggling to make the weight class his coaches and he know he would be most competitive at. He has heard of a diet drug that is claimed to REALLY work. Connor knows you are taking Introduction to Biochemistry so he comes to you and asks you for advice on whether he should try the drug.
The information Connor found online said that DNP had helped several people lose weight but that you needed to be careful with dosage. Some of the side effects included a fever, cataracts, and rashes. There were even some reports of deaths. DNP was said to be a mitochondrial uncoupler.
You tell Connor that you will look into it and get back to him. Your initial research determines that DNP is 2,4-dinitrophenol and has the following structure:
Question 1:
Based on the structure of DNP does it appear to be:
A. Mostly hydrophilic
B. Mostly hydrophobic
C. It is impossible to tell
You also learn that DNP can donate protons and has a pKa of 4.114, thus is classified as a weak acid.
Question 2:
You know from your biochemistry course that a proton gradient forms in the mitochondria, which statement best describes this?
A. There is a greater [H+] in the intermembrane space, between the outer and inner mitochondrial
membranes.
B. There is a greater [H+] in the mitochondrial matrix, inside the inner membrane.
C. There is a greater [H+] in the cytosol surrounding the mitochondria, outside the outer membrane.
D. Under normal conditions there isn’t a gradient, the [H+] is equal in all parts of the mitochondria.
Question 3:
Based on this information and the fact that DNP is labeled as a mitochondrial uncoupler, which of the following statements would best describe DNP’s mechanism of action?
A. DNP dissolves in the outer mitochondrial membrane and allows protons to flow into the cytosol,
thus negating the gradient.
B. DNP dissolves in the intermembrane space and binds protons, thus negating the gradient.
C. DNP dissolves in the inner mitochondrial membrane and allows protons to flow into the matrix,
thus negating the gradient.
D. DNP flows freely between all compartments of the mitochondria and carries protons with it, thus
negating the gradient.
Question 4:
By negating the proton gradient in the mitochondria, what does DNP uncouple?
A. Electron transport from ATP synthesis
B. Reduction of oxygen to water from ATP synthesis
C. Generation of NADH and FADH2 during metabolism from ATP synthesis
D. All of the above
E. Nothing, the description is misleading
In the searches you have done you find a research article describing an experiment where muscle cells grown in culture were exposed to DNP and the rate of ATP production and glucose oxidation were measured and the following data were obtained:
At this point Connor comes back to you and asks “Will it work? Will I lose weight if I take DNP?”
Question 5:
Which of the following is the most accurate answer given the information you have gathered?
A. Yes, you could lose weight because it would require your body to burn more fuel (ie. glucose,
fats, etc…) to produce the ATP your body needs.
B. Yes, you could lose weight because your body would produce less ATP so you wouldn’t adsorb as
many nutrients from your food.
C. No, you probably wouldn’t lose weight because your body would produce less ATP so you
wouldn’t be able to exercise as much.
D. No, you probably wouldn’t lose much weight because it only affects the mitochondria and they are really tiny and don’t contribute to your overall weight much.
OH NO NO2 NO 2,4-Dinitrophenol (DNP) NOExplanation / Answer
1- From the structure of the DNP we can confer that it's a hydrophilic compound. It has Nitrogen and oxygen which make it's hydrophilic as they are an electronegative group which can form Hydrogen-bond with water. So the answer is option A
2- the correct answer is option A- here is a greater [H+] in the intermembrane space, between the outer and inner mitochondrial membranes. These protons are used by ATP synthase for the synthesis of ATP during oxidative phosphorylation
3- the correct answer is option B- DNP dissolves in the intermembrane space and binds protons, thus negating the gradient.
DNP hinders the electron transport as a result of it proton is not transported into the intermembrane space.
4- Correct answer is option A- Electron transport from ATP synthesis.
5- From the given graph we can conclude that we need more glucose to produce the ATP. So we do more exercise we will need more glucose or fat as during the exercise the ATP required is more that then resting period.
So the correct answer is option A - Yes, you could lose weight because it would require your body to burn more fuel (ie. glucose, fats, etc…) to produce the ATP your body needs.