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The cytochrome P450 family of monooxygenase enzymes are involved in the clearance of drugs/medications from our body. Many adverse drug-drug interactions are known to occur as a result of interaction with the cytochrome P450 enzymes. A large number of drugs are metabolized by the enzyme P450 3A4. Human P450 3A4 is known to metabolize midazolam, a sedative, to a hydroxylated product, 1'- hydroxymidazolam. The kinetic data shown below are for the reaction catalyzed by P450 3A4. a. Focusing on the first 2 columns, determine the Km and Vmax for the P450 3A4 enzyme. b. Ketoconazole, an antifungal drug, is known to cause adverse drug interactions when taken along with midazolam. Using the data in the table, determine the type of inhibition caused by ketoconazole. Explain how you arrived at your answer. Midazolam (uM) 1 2 4 8 Rate of product formation (pmol min-1) 100 156 222 323 Rate of product formation in presence of ketoconazole pmol min-1) 11 18 27 40

The cytochrome P450 family of monooxygenase enzymes are involved in the clearance of drugs/medications from our body. Many adverse drug-drug interactions are known to occur as a result of interaction with the cytochrome P450 enzymes. A large number of drugs are metabolized by the enzyme P450 3A4. Human P450 3A4 is known to metabolize midazolam, a sedative, to a hydroxylated product, 1'- hydroxymidazolam. The kinetic data shown below are for the reaction catalyzed by P450 3A4. a. Focusing on the first 2 columns, determine the Km and Vmax for the P450 3A4 enzyme. b. Ketoconazole, an antifungal drug, is known to cause adverse drug interactions when taken along with midazolam. Using the data in the table, determine the type of inhibition caused by ketoconazole. Explain how you arrived at your answer. Midazolam (uM) 1 2 4 8 Rate of product formation (pmol min-1) 100 156 222 323 Rate of product formation in presence of ketoconazole pmol min-1) 11 18 27 40

Biochemistry
Biochemistry
9th Edition
ISBN:9781319114671
Author:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Publisher:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Chapter1: Biochemistry: An Evolving Science
Section: Chapter Questions
Problem 1P
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The cytochrome P450 family of monooxygenase enzymes are involved in the clearance of drugs/medications from our body. Many adverse drug -drug interactions are known to occur as a result of interaction with the cytochrome P450 enzymes. A large number of drugs are metabolized by the enzyme P450 3A4. Human P450 3A4 is known to metabolize midazolam, a sedative, to a hydroxylated product, 1'- hydroxymidazolam. The kinetic data shown below are for the reaction catalyzed by P450 3A4. a. Focusing on the first 2 columns, determine the Km and Vmax for the P450 3A4 enzyme. b. Ketoconazole, an antifungal drug, is known to cause adverse drug interactions when taken along with midazolam. Using the data in the table, determine the type of inhibition caused by ketoconazole. Explain how you arrived at your answer. Midazolam (uM) 00 AN1 2 14 8 Rate of product formation (pmol min-1) 100 156 222 323 Rate of product formation in presence of ketoconazole pmol min-1) 11 18 27 40
Transcribed Image Text:The cytochrome P450 family of monooxygenase enzymes are involved in the clearance of drugs/medications from our body. Many adverse drug -drug interactions are known to occur as a result of interaction with the cytochrome P450 enzymes. A large number of drugs are metabolized by the enzyme P450 3A4. Human P450 3A4 is known to metabolize midazolam, a sedative, to a hydroxylated product, 1'- hydroxymidazolam. The kinetic data shown below are for the reaction catalyzed by P450 3A4. a. Focusing on the first 2 columns, determine the Km and Vmax for the P450 3A4 enzyme. b. Ketoconazole, an antifungal drug, is known to cause adverse drug interactions when taken along with midazolam. Using the data in the table, determine the type of inhibition caused by ketoconazole. Explain how you arrived at your answer. Midazolam (uM) 00 AN1 2 14 8 Rate of product formation (pmol min-1) 100 156 222 323 Rate of product formation in presence of ketoconazole pmol min-1) 11 18 27 40
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