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First published on June 28, 2007; DOI: 10.1124/dmd.107.015743

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Received for publication March 12, 2007.
Revised June 25, 2007.
Accepted for publication June 25, 2007.

Disparity in Holo/Apoprotein Ratios of Different Standards Used for Immuno-quantification of Hepatic Cytochrome P450 Enzymes

Helen Perrett 1, Zoe Barter 2*, Barry Jones 3, Hiroshi Yamazaki 4, Geoffrey Tucker 2, Amin Rostami-Hodjegan 2

1 University of Sheffield 2 University of Sheffield and Simcyp Ltd 3 Pfizer 4 Showa Pharmaceutical University

* Address correspondence to: E-mail: z.barter{at}shef.ac.uk

Abstract

An analysis of reported hepatic abundances of CYP3A4 and 3A5 indicated that values determined by immunoquantification using commercially available, unpurified recombinant enzymes as standards are significantly lower than those determined using purified enzymes or human liver microsomes characterised using lysozomal peptides (CYP3A4: mean 45 vs 121 pmol/mg protein, p < 0.01; CYP3A5: mean 28 vs 83 pmol/mg protein, p < 0.05). When immunoquantifying CYPs it is assumed that the holo/apoprotein ratio is the same in the samples and the standard. Estimates of holo/apoprotein ratios from data reported for a range of CYPs purified from human liver and non-commercial recombinant systems indicated less than complete and variable haem coupling dependent on enzyme and system.


Key words: human CYP enzymes, in vitro-in vivo scaling, liver microsomes, recombinant proteins


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