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Stammerjohn, S

site of sequence variation) SNP (Single Nucleotide Polymorphism) Gene: ATG-GGA-TGC-TAA met-gly-cys-STOP SNP: ATG-GCA-TGC-TAA met-ala-cys-STOP Impact of new allele Alter protein function Alter protein structure or stability No consequence CYP2D6 and Codeine Example #1 Codeine Analgesic Prodrug CYP2D6-mediated bioactivation critical for analgesic effect 200mg codeine is equivalent to 30mg morphine (~10%) CYP2D6 More Lipophilic More Hydrophilic CYP2D6 Drug metabolizing enzyme Member of the P450 family (Cytochrome P450 2D6) Common substrates Beta-blockers (Metoprolol) SSRIs (Fluoxetine) Opiods (Codeine) SERMs (Tamoxifen) Highly polymorphic enzyme Over 100 reported Rowland et al, JBC (2006) 281:7614-7622 Allele Kinetic Data Kinetic plot of product formation versus substrate concentration for metabolic turnover of codeine catalyzed by highly purified recombinant CYP2D6 isoforms in vitro

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