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P450 AND METABOLISM IN TOXICOLOGY
Citation:
Petersen*, D. P450 AND METABOLISM IN TOXICOLOGY. Presented at P&G Health Care Research Center, Mason, OH, 8/14/2001.
Description:
The cytochromes P450 catalyze the initial phase of detoxification of many environmental chemicals, xenobiotic, drugs and the secondary metabolic product of plants. Plant secondary chemicals can be highly toxic, and they evolved in a coevolving plant - animal warfare - the plants are winning! Many detoxifications are accompiished by a two-step process. Phase I is often an oxidation step that adds or uncovers a reactive intermediate; Phase II is often a conjugation step that adds a hydrophilic group such as glucose, glutathione, sulfate or acetate, facilitating its clearance by the kidney. In may cases the phase I product is highly reactive and unless closely coupled to a phase II process, the reactive intermediates can mutate DNA. Human individuals have vastly different P450 profiles (many showing ethnic patterns) that predict sensitivity and relative toxicity, One gene (CYPIAI) will be shown that predicts lung (and other) cancers in certain ethnic groups. Another gene(CYP2D6) will be revealed to explain the different pharmacologic outcomes in dextromethorphan overdose.