ISBN: 978-83-60043-10-3 - eurobic9

Eurobic9, 2-6 September, 2008, Wrocław, Poland
PL8. Cytochromes P450 And Diversity : Adaptation of Living Organisms to
Their Chemical Environment
D. Mansuy
Chemistry and Biochemistry, UNIVERSITE PARIS DESCARTES, 45 rue des Saints-Péres, 75270, PARIS,
France
e-mail: daniel.mansuy@univ-paris5.fr
Living organisms exhibit a spectacular ability to adapt themselves to an always changing chemical environment.
The pathways that have been selected by life evolution for aerobic organisms to metabolize and eliminate
xenobiotics are strikingly similar. The first step of xenobiotics metabolism is most often catalyzed, in all aerobic
organisms, by a multigene family of hemeproteins, the cytochromes P450(P450s). The P450s responsible for
xenobiotics metabolism are able to catalyze the monooxygenation of a huge amount of compounds exhibiting an
extreme diversity of structures. Consequently, most often, those P450s exhibit a very poor substrate selectivity ;
however they act as efficient catalysts and, very often, lead to regioselective hydroxylations of their substrates.
How is it possible to explain this “paradox”, which is a key element in our adaptation to variable chemical
environments? Recent X-ray structures of mammalian P450s, published during these last four years allow one to
start to understand the molecular basis of the adaptation of P450s to xenobiotics for the most possible efficient
oxidation catalysis. The corresponding recent data will be presented after a brief overview of 50 years of
research on P450s (P450 has been discovered in 1958), illustrating the species, substrate, reaction, and
coordination chemistry diversity of these enzymes . Finally, the possible future of P450 research will be
discussed on the basis of quite recent preliminary results
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