Suggest a reason why the drug might affect the two girls differently.
1b. What tests might Dr. Ryder order to determine why the two girls are reacting as they are to the drug? Provide two or three appropriate examples of tests.
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Part II – Enzyme Activity Dr. Ryder learns that the difference in patient reaction to the drug probably has something to do with how the drug is naturally metabolized in the body to be removed as waste. After searching the scientific literature, she learns that the drug 6-MP can either be converted to the active form, TGN nucleotides, or can be inactivated with the help of the TPMT enzyme (thiopurine methyltransferase). Within each patient who takes the drug, both processes are occurring and they compete with each other.
Figure 1. Flow Chart Flow chart showing activiation and inactivation paths of the drug 6-MP.
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Since the therapy aims to harm rapidly replicating cells without overly impacting normal ones, it is important that excess drug is inactivated. Dr. Ryder decides to see how levels of the TPMT enzyme activity might vary between people.
She reviews the research papers that have been published about the TPMT enzyme and finds an interesting graph. From a study of 298 randomly selected Caucasian individuals, researchers found the following levels of TPMT enzyme activity:
Figure 2. Simplified Results. Simplified bar graph showing results from a study of 298 randomly selected Caucasian patients.