Foreign compounds and intermediary metabolism: sulfoxidation bridges the divide.
It is widely appreciated that as a xenobiotic travels through an organism and interacts with the biochemical machinery of a living system, it most probably will undergo a number of metabolic alterations usually leading to a cluster of differing chemical species. Indeed, the modern 'metabonomic' approach, where earlier studied drug metabolism profiles have been reassessed, has indicated that there are normally many more previously unrecognised minor metabolites, and when all such biotransformation products are considered, then their total number is legion. It is now being recognised also that the same metabolic alteration of a substrate, especially a xenobiotic substrate, may be catalysed by more than one enzyme and that the previously sacrosanct notion of an enzyme's 'substrate specificity' may well be inverted to read a substrate's 'enzyme preference'. The following brief article attempts to highlight another aspect where our general acceptance of the 'status quo' needs to be reconsidered. The conventionally acknowledged division between the collection of enzymes that undertake intermediary metabolism and the group of enzymes responsible for xenobiotic metabolism may be becoming blurred. It may well be a prudent time to reassess the current dichotomous view. Overcoming inertia, with a realignment of ideas or alteration of perception, may permit new concepts to emerge leading to a more profound understanding and hopefully eventual benefits for mankind.
Department of Biomolecular Medicine, SORA Division, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, South Kensington, London SW7 2AZ, UK. s.c.mitchell@imperial.ac.uk
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D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D004299:Dopamine beta-Hydroxylase / Q000502:physiology; D006801:Humans; D010651:Phenylalanine Hydroxylase / Q000502:physiology; D013454:Sulfoxides / Q000378:metabolism*; D015262:Xenobiotics / Q000378:metabolism*
D013454:Sulfoxides; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D010651:Phenylalanine Hydroxylase; D004299:Dopamine beta-Hydroxylase