Expression Of Mutant CYP2D6 Plasmids For Analysis Of The Structure/Function Of Substrate Access Channels In CYP2D6
Halcisak, Justin M.
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Cytochrome P450s are enzymes produced by the body that play an important role in metabolism. CYP2D6, a member of the cytochrome P450 family, is responsible for a large portion of the metabolism of drug compounds and other xenobiotic compounds. The CYP2D6 enzyme is one of the less frequently occurring P450s but accounts for almost a fourth of all drug metabolism in the body. Examining the structural properties of CYP enzymes involved in regulating the interactions between the protein and substrates are crucial in understanding the role of P450s in drug degradation. These reactions involve the binding of substrate and oxygen in the active site deep within the P450. The redox reactions by CYPs are used in degradation and metabolism of both synthetic and natural xenobiotic compounds. The regulation of CYPs activity is crucial to avoid negative effects and increased toxicity in the body. The interactions with compounds moving within the protein are believed to participate in regulating CYP activity. Studies into the movement of substrates through the enzyme and the active site may indicate the importance of egress channels. It is believed that the amino acid structure of the enzyme near the egress channel, or where the catalyzed substrate exits the protein, can directly influence the reaction rate of the enzyme. Further experiments of point mutations and studies of these potential egress channels in CYP2D6 are needed to fully understand the factors that regulate drug metabolism.