ArticleDrug metabolism and pharmacokinetics2012
Comparison of CYP3A4 and CYP3A5: the effects of cytochrome b5 and NADPH-cytochrome P450 reductase on testosterone hydroxylation activities.
Article in Drug metabolism and pharmacokinetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 20 citations in OpenAlex.
- The Mechanism-Based Inactivation of CYP3A4 by Ritonavir: What Mechanism?International journal of molecular sciences · 2022Review
- Relation of Transcriptional Factors to the Expression and Activity of Cytochrome P450 and UDP-Glucuronosyltransferases 1A in Human Liver: Co-Expression Network Analysis.The AAPS journal · 2017Article
- Differential Regulation of CYP3A4 and CYP3A5 and its Implication in Drug Discovery.Current drug metabolism · 2017Review
- CytochromeMonatshefte fur chemie · 2017Article
- Effect of CYP3A5 expression on the inhibition of CYP3A-catalyzed drug metabolism: impact on modeling CYP3A-mediated drug-drug interactions.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
CYP3A4 and CYP3A5 require cytochrome b5 (b5) and NADPH-cytochrome P450 oxidoreductase (CPR) for optimum metabolism, but little is known about the specific requirements for b5 and CPR to produce optimal activities for these enzymes. The metabolism of testosterone (TT) by CYP3A4 and CYP3A5 was analyzed by various combinations of b5 and CPR using a fixed amount of recombinant P450 which had been purified from an Escherichia coli expression system. CYP3A4 and CYP3A5 required 4- and 8-fold more of CPR than of the P450s, respectively, for optimal activity. The requirement of b5 for optimal activity showed the same pattern for both CYP3A4 and CYP3A5, exhibiting a gradual stimulation of the activity reaching a maximum at 16 fold more b5 than P450. Although CYP3A4 exhibited higher activities than CYP3A5 in all combinations, both enzymes exhibited the same dependency profile for b5 and CPR. Therefore, the stronger activity of CYP3A4 compared to CYP3A5 appears to be intrinsic to the CYP3A4 protein itself and not to different requirements for b5 and CPR. Since the relative amounts of b5 and CPR are important in the maintenance of CYP3A4 and CYP3A5 activities, different levels of these proteins in vitro and in vivo may cause altered metabolism of their substrates or misinterpretation of enzyme properties.
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Registered trials
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