Cytochrome P450 enzymes are a class of enzymes often found in the liver and involved in metabolizing compounds in preparation of expulsion by the kidneys. While the actual inhibition and activation of P450s is complicated (with complexities seemingly added in in vivo studies that are missing from in vitro experiments), we will assume a relatively simple model, specifically of cytochrome P540 3A4 (CYP3A4), which is involved in metabolizing a large percentage of medications. For our simplified model, we will assume that inhibitors and activators affect the ability of CYP3A4 to bind and interact with the substrate, following similar kinetics as that of hemoglobin.

a. Draw the suggested curve for CYP3A4 with increasing concentrations of one of its substrates, diazepam. Include changes in the curve for an inhibitor and an activator.

b. A patient who takes diazepam nightly for her anxiety comes into the emergency room with bronchitis. The antibiotic prescribed is erythromycin, which is, though a potential substrate of CYP3A4, is also an inhibitor of the enzyme. What are the potential side effects for this patient being on both of these at the same time? Explain.

c. Cyclosporin is another substrate of CYP3A4. The same patient in part (b) after disliking the side effects that came with diazepam has switched to an herbal supplement, St. John’s Wort, a known activator of CYP34A. Since St. John’s Wort is an herbal supplement, and the patient does not consider it "medication," she fails to put this on any of her paperwork or medical history. If this patient undergoes a kidney transplant and is given cyclosporin to help her body not reject the organ, what are the potential side effects? Explain.