Cytochrome P450 enzymes, especially those of the CYP3A family, play a major role in the metabolism of many drugs.' Patient response to drugs metabolized by CYP3A4 and CYP3A5 varies considerably and part of this variability is due to genetic polymorphism ot the CYP3A5 enzyme. In this study, human liver microsomes (HLM) were prepared from a panel of 26 liver samples and total soluble protein was evaluated. The CYP3A5 and CYP3A4 protein contents were determined by Western blotting and metabolic studies of individual HLM were performed with three selected substrates, ALP, MDZ and TST using HPLC. Results from the 26 HLM preparations revealed a high variability in CYP3A4 (366.7-1.06 pmol/mg protein, 346 fold) and CYP3A5 (4.26 -0.14 pmol/mig protein, 30 fold) content. As might be expected, the two samples with the CYP3A5*l/*3 genotype expressed higher CYP3A5 protein level than the other 24 samples (CYP3A5*3/*3) indicating the consequence of the CYP3A5*1 allele on CYP3A5 protein expression.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:492887 |
| Date | January 2008 |
| Creators | Sethabouppha, Benjabhorn |
| Publisher | University of Manchester |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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