• Corpus ID: 21244198

Specificity of substrate and inhibitor probes for human cytochromes P450 1A1 and 1A2.

  title={Specificity of substrate and inhibitor probes for human cytochromes P450 1A1 and 1A2.},
  author={Wichittra Tassaneeyakul and Donald Birkett and M. E. Veronese and Michael E. McManus and Robert H. Tukey and Linda C. Quattrochi and H. V. Gelboin and John O. Miners},
  journal={The Journal of pharmacology and experimental therapeutics},
  volume={265 1},
Kinetic and inhibitor studies using cDNA-expressed enzymes and human liver microsomes have characterized the specificity of a range of cytochrome P450 (CYP) 1A substrate and inhibitor probes towards the two isoforms comprising this subfamily. Expressed CYP1A1 and CYP1A2 both catalyzed the O-deethylation of phenacetin, although the apparent Km was about 4-fold lower for CYP1A2 (25 vs. 108 microM). Phenacetin O-deethylation exhibited biphasic kinetics in human liver microsomes, and the apparent… 

Differential selectivity of cytochrome P450 inhibitors against probe substrates in human and rat liver microsomes.

It is evident that CYP inhibitors do not exhibit the same selectivity in human and rat liver microsomes, due to differential selectivity of the inhibitors and/or differences in the CYP isoform responsible for metabolism in the different species.

Specificity of substrate and inhibitor probes for cytochrome P450s: evaluation of in vitro metabolism using cDNA-expressed human P450s and human liver microsomes.

The results indicated that substrates and inhibitors reported as P450 selective probes are not necessarily specific for individual human P450 forms.

Involvement of CYP2E1 as A low-affinity enzyme in phenacetin O-deethylation in human liver microsomes.

Results suggest that CYP2E1 is responsible for the low-affinity component of POD in human liver microsomes.


Results suggest that CYP2E1 is responsible for the low-affinity component of POD in human liver microsomes, and is used to assess the catalytic activity of CYP1A2 in vivo and in vitro.

Involvement of Human CYP 1 A Isoenzymes in the Metabolism and Drug Interactions of Riluzole In Vitro 1

In vivo, riluzole is unlikely to exhibit significant pharmacokinetic drug interaction with coadministered drugs that undergo phase I metabolism, and is predominantly metabolized by CYP1A2 in human hepatic microsomes to N-hydroxyriluzoles; extrahepatic CYP 1A1 can also be responsible for the formation of several other metabolites.

Human cytochromes P450 mediating phenacetin O-deethylation in vitro: validation of the high affinity component as an index of CYP1A2 activity.

CYP1A2 is the only high affinity human liver phenacetin O-deethylase, thereby validating the use of the high affinity component as an index of CYP 1A2 activity in human liver microsomes.

CYP 2 A 13 Metabolizes the Substrates of Human CYP 1 A 2 , Phenacetin , and Theophylline

  • Biology, Chemistry
  • 2007
The present study investigated the substrate specificity of CYP2A13 and found that it has higher affinity toward phenacetin than CYP1A2, and is much more active for nicotine, cotinine, and especially 4-(methylnitrosamino)-1(3-pyridyl)-1-butanone metabolisms.

Characterization of the selectivity and mechanism of human cytochrome P450 inhibition by the human immunodeficiency virus-protease inhibitor nelfinavir mesylate.

The results suggest that the probable mechanism for CYP3A4 inhibition by nelfinavir is a transient metabolic intermediate or stable metabolite that coordinates tightly but reversibly to the heme moiety of the P450.

A significant role of human cytochrome P450 2C8 in amiodarone N-deethylation: an approach to predict the contribution with relative activity factor.

According to the concept of relative activity factor, it was clarified that CYP2C8 as well as CYP3A4 were significantly involved in amiodarone N-deethylation in human livers at clinically significant concentrations and that the contributions of CYP1A2, CYP 2C19, and CyP2D6 were relatively minor.