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Many of the drugs we use to combat infections by microorganisms act as enzyme inhibitors. If you were engaged in developing new antimicrobial drugs, how might you proceed to develop new enzyme-inhibiting drugs knowing what you do about microbe metabolism?

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Casey Durgan
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4 Mar 2019

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1.What does it mean for a bacterium to be “antibiotic resistant”? In your opinion, what factors have led to the development of antibiotic resistant bacteria?

2. How does Penicillin work? In what other ways might Penicillin (and similar drugs) be used to inhibit a bacterium’s ability to cause infection or persist in a host? (HINT: Think about the other structural features of a bacterium)

3. Antibiotic resistance is a serious threat to human health. What role do beta-lactamases have in increasing bacterial resistance to drugs such as penicillin? In the future, do you feel we will be able to “solve” the antibiotic resistance problem?

Dewey Cheatham is the new Vice President of Marketing for a large online search engine company, Pottstown Innovative Enterprises (AKA, PIE). Dewey has been doing some research into how he can increase the Company’s revenues and thereby really impress the Company brass. During his research he came across an article about Brazilian pharmacies looking for an advertising vehicle to tap into the U.S. consumer market. Further research reveals that this could be a billion dollar venture and if PIE plays its cards right, it could make a substantial amount of money given its extensive advertising network. Dewey is super ecstatic about the possibilities and is salivating over what this could mean for his career with PIE.

Before Dewey pulls the trigger on this, he decides to consult with his legal department. The legal department tells Dewey the following:

1. The shipment of prescription drugs from pharmacies outside the United States to customers in the United States may violate the Federal Food, Drug and Cosmetic Act and in the case of controlled prescription drugs, the Controlled Substances Act.

2. The FDA cannot ensure the safety and effectiveness of foreign prescription drugs that are not FDA-approved.

3. Imported drugs typically do not meet FDA’s labeling requirements and may not have been manufactured, stored and distributed under proper conditions; and may not have been dispensed in accordance with a valid prescription.

4. The government has historically been very lax in enforcing the laws in this area and legally there are a few gray areas; therefore the risk of any prosecution may not be significant.

After the consultation with Legal, Dewey is confused as to what his decision should be. If you were advising Dewey on the ethical implications presented by this case, what would you say to him? Specifically, what ethical problems and issues do you see?

How does temperature affect enzyme activity? SPECIFICALLY what happens at low temperatures? Why do we store enzymes in the freezer? What is the “optical temperature” of an enzyme? Approximately what might this temperature be for human enzymes (in Celcius!)? Approximately what might be the optimal temperature for the fungus that grows on the food that you forget about in the back of the refrigerator?

What is competitive inhibition? How do competitive inhibitors affect enzyme activity?

What are non-competitive inhibition? How do these affect enzyme activity?

Given what you know about the relationship between the structure and function of enzymes, what specific aspects of protein structure are affected by the two types of competitors? Explain using the terminology that you learned about the levels of protein structure.

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