Synthesis of cytochrome P450 inhibitors of vitamin E metabolism |
Posted on:2007-05-14 | Degree:M.Sc | Type:Thesis |
University:Brock University (Canada) | Candidate:Ohnmacht, Stephan Alexander | Full Text:PDF |
GTID:2444390005469716 | Subject:Chemistry |
Abstract/Summary: | |
Vitamin E is a group of eight different tocopherols and tocotrienols distinguished by the degree of methylation of the aromatic ring. The North American diet contains more gamma-tocopherol than the more biologically active alpha-tocopherol. gamma-Tocopherol has recently been shown to have several advantages over its more heavily studied alpha-analogue such as the trapping of electrophilic mutagens such as peroxynitrite. Cytochrome P450 preferentially metabolizes gamma-tocopherol over all other tocopherols beginning with an o-hydroxylation on the phytyl side chain. Whether a single enzyme (CYP4F2) or several isozymes (such as the CYP3A family) are responsible for this action has remained controversial. We herewith report the synthesis of a highly potent inhibitor of the oxidative metabolism of tocopherols and tocotrienols and the subsequent biological testing in human cell lines to determine the active enzyme of vitamin E metabolism. |
Keywords/Search Tags: | Cytochrome P450, Tocopherols and tocotrienols |
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