Case Study Section 3 – Ox. Phos. Based on “Wrestling with Weight Loss: The Dange
ID: 89787 • 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:
You also show Connor a clinical report you found about another wrestler, Charles, that used DNP to lose weight quickly who ended up taking a double dose because he was afraid he wouldn’t make his weigh-in. Charles was admitted to the hospital with symptoms including: being flushed, breathing fast, excessive sweating, nausea, and weakness in his knees. Charles had experienced an overdose of DNP, which caused all of his symptoms.
Question 6:
Charles’s flushed face and sweating were caused by a high fever. What is the most likely explanation for the fever?
A. The lack of a mitochondrial proton gradient caused the mitochondria to become sick and die,
thus causing the fever.
B. The protons used to make the gradient have energy associated with them that normally drives
ATP synthesis but when the gradient is negated by DNP the energy is released as heat.
C. DNP was recognized as non-self by Charles’s immune system and a fever was part of the defense
mechanism.
D. The fever had nothing to do with his taking DNP, he was just sick.
Question 7:
What is the best explanation for Charles’s rapid breathing during the DNP overdose?
A. He was hyper ventilating in response to less oxygen entering his body.
B. The heavy breathing was all in response to his fever, like panting in a dog.
C. His electron transport chain had increased activity to off-set the protons transported by DNP so more oxygen was required to accept the electrons, the rapid breathing was his body’s way to try
to get more oxygen.
D. He was excited about his weight loss and upcoming match.
Question 8:
What is the best explanation for Charles’s weakness and nausea?
A. The lack of ATP being produced by Charles’s muscles in response to the DNP made muscle
contraction more difficult, thus the weakness.
B. Increased rates of metabolism to off-set the actions of the DNP caused a drop in blood glucose
causing both weakness and nausea.
C. Both A and B are likely explanations.
D. Charles was just excited about his weight loss and nervous about his upcoming match.
You explain all these risks to Connor but he isn’t convinced. He remembers hearing about a protein called Uncoupling Protein in his freshman biology class that functions similarly to DNP. He argues that if a naturally occurring protein does the same thing how can DNP be dangerous?
Question 9:
Which of the following would be the most appropriate explanation?
A. Uncoupling proteins are not expressed in humans.
B. Uncoupling proteins have a very different mode of action than DNP.
C. Uncoupling proteins only exist in a tissue called brown adipose tissue that only exists in infants.
D. Uncoupling proteins are highly regulated and only active when needed and not to the excess of
causing problems while DNP has no regulation beyond how much you take.
Question 10:
Which of the following would be situations when uncoupling proteins would be active (select all that apply)?
A. A hibernating bear
B. A dog in the summer trying to rid itself of excess heat
C. A mouse at room temperature (note that thermoneutral for a mouse is ~30°C)
D. A premature infant with very little fat stores
E. An adult human at maintenance (ie.at a healthy body weight and not gaining or losing weight)
F. An adult human post-Thanksgiving dinner (ie. much greater Caloric intake than normal)
OH NO NO2 NO 2,4-Dinitrophenol (DNP) NOExplanation / Answer
6. Answer is B. DNP decrease the formation of high energy phosphate bond in mitochondria and at the same time systemic oxygen consumption or uncoupling of oxidative phosphorylation. DNP also act as chemical ionophore, stopping the final energy conversion by exporting proton ion needed for ATP production across the mitochondrial membrane by increasing the basal leak of proton. This shift in proton electrochemical gradiant result in potential energy dessipating as a heat leading to fever.
7. Answer is C. Due to uncoupling of oxidative phosphorylation and systemic oxygen consumption leads to requirement of more oxygen result into rapid breathing.
8. Answer is C. Due to disturbed oxidative phosphorylation lack of ATP production and stimulation of glycolysis leads to weakness and nausea.
9. Answer is D. Uncoupling proteins are highly regulated and activated only when required so not causes the effect like DNP .
10. A hibernating bear when body require excess heat, An adult human post thanksgiving dinner are the situation in the presence of uncoupler.