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Managing Biotransformation: Introduction and Overview

Jeffrey Bland, PhD, FACN

A description of the family of human detoxification enzymes, cytochrome P450s, first appeared in the literature in 1962.1 Until that time it was known that foreign compounds were somehow detoxified by specific physiological processes, but the nature of these processes had not been elucidated. In the absence of an understanding about this superfamily of detoxification enzymes (now known to be generated by 57 genes, many of which show multiple polymorphisms), there was much speculation as to how an individual actually eliminated lipophilic compounds, both exogenous and endogenous. It is now recognized that the enzymes in the CYP450 superfamily have roles not only in the detoxification of drugs and other xenobiotics, but also in the metabolism of nutrients and endogenous molecules such as essential fatty acids, phytonutrients, steroid hormones, and vitamins D and A.2

Over the past 40 years, we have learned that what is termed phase 1 activation of lipophilic compounds is carried out by enzymes in the CYP450 family. This phase 1 biotransformation of a molecule creates an activated intermediate that is either directly eliminated from the body or, more commonly, becomes a substrate for one of the phase 2 conjugation enzymes and is then eliminated. The phase 2 conjugases, which include sulfation, amino acid conjugation, glutathione conjugation, glucuronidation, methylation, and acetylation activities, are also highly polymorphic. In both the phase 1 and phase 2 detoxification enzyme families, some enzymes are constitutively expressed and some are inducible. Importantly, certain environmental and nutritional agents have been found to influence the induction and activities of specific phase 1 and phase 2 enzymes.3,4

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