Which of the following statements about metabolism is TRUE:[Fill in the blank]

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Question: Which of the following statements about metabolism is TRUE:[Fill in the blank]

Options:
 a. Most phase II metabolism occurs in the kidneys.
 b. Most drugs require hepatic metabolism in order to activate them to exert their desired pharmacological activity.
 c. Drug metabolism refers to the direct removal of intact drug through the kidneys
 d. Cytochrome P450 enzymes are responsible for the phase I oxidation of many drug molecules.

Option a: 'Most phase II metabolism occurs in the kidneys.' This is incorrect. Phase II metabolism (conjugation reactions like glucuronidation, sulfation, acetylation, etc.) primarily occurs in the liver, with some participation in other tissues, but the kidneys are not the main site. The liver provides the necessary conjugating enzymes (e.g., UDP-glucuronosyltransferases) for most phase II processes. Misplacing this activity to the kidneys is a common misconception about the organ distribution of metabolism.

Option b: 'Most drugs require hepatic metabolism in order to activate them to exert their desired pharmacological activity.' This statement is misleading. While hepatic metabolism can convert prodrugs into active forms, many drugs exert effects in their parent (unmetabolized) form, and not all require metabolism for activity. Some drugs are active without needing hepatic activation, and others may be deactivated by metabolism. Therefore, this overgeneralizes the role of hepatic metabolism.

Option c: 'Drug metabolism refers to the direct removal of intact drug through the kidneys.' This is incorrect. Drug metabolism typically refers to chemical modification of the drug, often to more water-soluble forms to facilitate excretion. Direct renal excretion of intact drug is not metabolism; it’s elimination. Metabolism usually makes the molecule more polar, not removing it unchanged.

Option d: 'Cytochrome P450 enzymes are responsible for the phase I oxidation of many drug molecules.' This is correct. Cytochrome P450 enzymes (CYPs) carry out Phase I reactions, including oxidation, reduction, and hydrolysis, introducing reactive or polar groups into substrates. They are major contributors to drug metabolism, particularly oxidation reactions that prepare compounds for Phase II conjugation or excretion. This aligns with standard pharmacology/pharmacokinetics knowledge about metabolism.

In summary, evaluating each statement shows that a–c contain common misconceptions about where metabolism occurs, what it entails, or how it relates to drug activity, whereas option d accurately describes the role of CYP450 enzymes in Phase I oxidation of many drugs.

Which of the following statements about metabolism is TRUE:[Fill in the blank]

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