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Posted on April 6, 2016
Date - April 6, 2016
MS Thesis – 602
Title: “Cytochrome P450’s and the Effects of the Addition of Undecylenic Aldehyde.”
Cytochrome P450’s are vital enzymes for the metabolism of chemicals that are foreign to the human body. By altering the activity of these enzymes through enzyme inhibition, it is possible to alter rates of metabolism of these so-called xenobiotics many of which belong to the pharmaceutical class, resulting in what is termed a “Drug Interaction”. There are many well-known drug interactions known, though most involve inhibition of the human cytochrome P4503A4 enzyme. A classic example is the case of statins drugs and furanocoumarins found in grapefruit juice. Research aimed at determining the effects of foreign chemicals on human cytochrome P450’s is an important area of pharmacology and toxicology, as it has the potential to identify toxic or dangerous drug interactions before a drug reaches clinical trials. Toward this end, prior studies with aldehydes and terminal olefins have shown that both general classes of molecules can potentially destroy certain mammalian cytochrome P450 enzymes. The compound, undecylenic aldehyde, which is an additive in a variety of consumer products, contains both functional groups, and was therefore a target for evaluation in the current study. The effects of adding various concentrations of undecylenic aldehyde to different human P450 isoforms were monitored using HPLC-based enzyme assays, and the results showed a significant decrease in the activity of isoforms 2E1 and 3A4 in the presence of this compound. Modes of inhibition were analyzed through Michaelis-Menten kinetics and appeared to be reversible and non-competitive (mixed) in nature.