Question

Below is the chemical structure for a tuberculosis drug, Rifapentine. HO,, он OH OH J NH OH ° 3. RNA polymerase is a(n): a. Substrate b. Enzyme c. Product d. Mechanism 4. Describe the difference between bacteriostatic and bactericidal antibiotics. Below is national TB data from the CDC (https://www.cdc.gov/tb/statistics/reports/2022/state_local_data.htm): Washington 3.2 TB Incidence Rates* by Reporting Area, United States, 2022 1. Provide the total number of the following functional groups in this molecule: a. Alcohol b. Amine c. Ketone d. Carboxylic Acid e. Ether f. Ester The Campbell et al.¹ states, "Rifapentine is thought to inhibit bacterial DNA-dependent RNA polymerase, which appears to occur as a result of drug binding in the polymerase subunit deep within the DNA/RNA channel, facilitating direct blocking of the elongating RNA." 2. The excerpt above is an example of: a. Chemical Reaction Mechanism b. Bioavailability c. Mechanism of Action d. Metabolism California 4.7 Alaska 13.0 "Cases per 100,000 persons "Includes New York City Hawaii 7.0 Texas 3.7 New York 3.6' New Jersey 3.1 Maryland 2.5 Incidence rate <1.5 1.5-2.5 2.5-4.5 24.5 Campbell, Elizabeth A., et al. "Structural mechanism for rifampicin inhibition of bacterial RNA polymerase." Cell 104.6 (2001): 901-912. 5. What does incidence rate mean and why do we often use this metric as opposed to just number of cases? 6. The CDC also provides data for US territories (shown below). Explain how this data illustrates some of the TB inequities Dr. van de Water spoke about in her guest lecture: The TB incidence rates (cases per 100,000 persons) among the U.S. territories and freely associated states were: • Republic of the Marshall Islands, 252.1 • Federated States of Micronesia, 45.1 • Commonwealth of the Northern Mariana Islands, 44.7 • Republic of Palau, 38.8 • Guam, 34.9 Puerto Rico, 0.7 Data for American Samoa and the U.S. Virgin Islands are unavailable for 2022. One of the risks of taking isoniazid (TB antibiotic) is that it can act as a mild serotonin inhibitor, which has led isoniazid to be used as an antidepressant as well. If too much serotonin is inhibited, the patient may feel strong side effects (e.g., convulsions, fever, nausea, etc.). This inhibition is more likely if the patient eats food that trigger a histamine release. Thus, doctors usually tell patients on isoniazid to avoid foods like alcohol, bananas, tomatoes, chocolate, etc. 8. A reaction between isoniazid and histamine is shown in Q7 and below is the chemical structure of serotonin. Using this information, explain why the presence of histamine increases the likelihood of serotonin inhibition by isoniazid. NH2 N Isoniazid NH2 HN Histamine -NH2 -NH2 H₂N. NH₂ 7. Given the overall chemical reaction above, draw a plausible mechanism for this reaction. HO. Serotonin

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