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    Metabolizer phenotype of CYP2D6

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    I got 0 out of 15 points for my answer on this problem. I'm thinking I should have received some partial credit. I'm posting the original question, my answer, and the "official" answer. I understand that the given answer is a better method, but won't my proposed method work? I'm looking for some expert, detailed, technical advice to help me support my claim for partail credit.

    The Problem: Briefly describe the method that you would use to test an individual for metabolizer phenotype of CYP2D6. Be sure to include the name of the test compound, when and which biological fluid(s) to collect, which compound(s) to measure, and how to assess metabolizer phenotype. This description should be no longer than one paragraph, and should fit in the box below. Point will be taken off for overly long descriptions.

    My answer: CYP2D6 is a metabolic enzyme. Enzymes are proteins; therefore I'd use a Western Blot to analyze protein level alterations. A serum sample with the enzyme would be collected and tested with antibody for protein P. The genotypic results could be compared with other known CYP2D6 genotypes.

    My reasoning: Allele variants have specific base changes and amino acid changes. The procedure I proposed would identify these protein level alterations. Once the variant allele is identified, the activity level of the enzyme associated with the variant allele is known.

    Official answer: You would administer 5 mg of debrisoquine, measure the ratio of debrisoquine/4-OH debrisoquine in the urine at e.g., 5-8 hours. A poor metabolizer will have a high ratio whereas a rapid metabolizer will have a low ratio.

    Another answer: You would administer 30 mg of dextromethorpha measure the ratio of dextromethorphan/dextrorphan in the urine at e.g., 5-8 hours. A poor metabolizer will have a high ratio whereas a rapid metabolizer will have a low ratio.

    Correct drug: 4 pts (fail to mention the metabolite name: -1 pt)
    Mention urine (or plasma or serum): 1 pt
    Mention time (wait a period of time-okay): 1 pt
    Correctly discuss the ratio (drug/metabolite): 5 pt
    Correctly interpret the ratio to metabolizer phenotype: 5pt

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    Solution Preview

    There are basically two methods that can be used to identify a person as a poor metabolizer or a rapid metablizer based on the cytochrome P450 CYP2D6 enzyme. The first method is the one described by your instructor, and the second method is to genotype the individual and match them with known alleles. While it seems that you wanted to answer using the second method, your answer was incomplete and used incorrect methodology. Below I have pasted some test information from one of the laboratories ...

    Solution Summary

    The expert examines metabolizer phenotype of CYP2D6. The ratio is determined.