Multiple forms of human P450 expressed in Saccharomyces cerevisiae. Systematic characterization and comparison with those of the rat.

@article{Imaoka1996MultipleFO,
  title={Multiple forms of human P450 expressed in Saccharomyces cerevisiae. Systematic characterization and comparison with those of the rat.},
  author={Susumu Imaoka and T. Yamada and Toyoko Hiroi and K. Hayashi and Toshiyuki Sakaki and Yoshiyasu Yabusaki and Yoshihiko Funae},
  journal={Biochemical pharmacology},
  year={1996},
  volume={51 8},
  pages={
          1041-50
        }
}
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216 Citations
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216 Citations

Catalytic specificity of CYP2D isoforms in rat and human.

In rats, bufuralol 1'2'-ethenylation activity was specific to CYP2D4 and debrisoquine 4-hydroxylation and propranolol 7-hydroxyylation activities were specific toYP2D2, and these catalytic activities are useful as a probe for rat CYP1D isoforms.

CATALYTIC SPECIFICITY OF CYP 2 D ISOFORMS IN RAT AND HUMAN

This study investigated the catalytic specificity toward bufuralol, debrisoquine, and propranolol, which are frequently used as CYP2D substrates in rats and found these catalytic activities are useful as a probe for rat CYP1D isoforms.

Metabolism of Sesamin by Cytochrome P450 in Human Liver Microsomes

A good correlation was observed between sesamin catecholization activity and CYP2C9-specific activity in in vitro studies using 10 individual human liver microsomes, strongly suggesting that CYP 2C9 is the most important P450 isoform for sesamination catechlization in human liver.

Contribution of human hepatic cytochrome P450s and steroidogenic CYP17 to the N-demethylation of aminopyrine.

It is suggested that several human hepatic P450s, especially CYP2C19, and steroidogenic CYP17 exhibit aminopyrine N-demethylase activity.

Enzymatic properties of human CYP2W1 expressed in Escherichia coli.

Expression of cytochrome P450 2A6 in Escherichia coli: purification, spectral and catalytic characterization, and preparation of polyclonal antibodies.

  • P. Souček
  • Biology, Chemistry
    Archives of biochemistry and biophysics
  • 1999
Rabbit polyclonal antibodies were produced against recombinant CYP2A6 and proved to be very useful for immunoblotting and immunoinhibition studies and availability of this expression system and specific antibodies should facilitate characterization of the role of CYP 2A6 in the metabolism of chemicals and in the study biological relevance of genetic polymorphisms of this enzyme.

Establishment of a yeast system that stably expresses human cytochrome P450 reductase: application for the study of drug metabolism of cytochrome P450s in vitro.

Cloning and expression of rat CYP2E1 in Saccharomyces cerevisiae: Detection of genotoxicity of N‐alkylformamides

It is demonstrated that the 2E1‐expressing cells metabolize the two N‐alkylformamides to genotoxic intermediates and, therefore, they provide an useful tool to study the bioactivation mechanism of potential P450 2 E1 substrates.

Amino acid residues affecting the activities of human cytochrome P450 2C9 and 2C19.

The results suggest that residues in substrate recognition site (SRS) 3 and 4 are important for the substrate specificity, whereas His99 is important in the substrate binding of CYP2C19.

Cytochrome P450 2D catalyze steroid 21-hydroxylation in the brain.

The results support the idea that CYP2D4, not P450c21, works as steroid 21-hydroxylase in the brain, and that this regulation is modified by central nervous system-active drugs such as fluoxetine.
...

References

SHOWING 1-10 OF 40 REFERENCES

Isolation and characterization of human liver cytochrome P450 2C19: correlation between 2C19 and S-mephenytoin 4'-hydroxylation.

This is the first demonstration of the expression of 1C19 at the enzyme level, and correlation studies suggest that 2C19 plays a role in the 4'-hydroxylation of S-mephenytoin.

Expression of modified human cytochrome P450 2E1 in Escherichia coli, purification, and spectral and catalytic properties.

The development of a system for relatively high-level expression of human cytochrome P450 2E1 in Escherichia coli is reported, and the highest levels of expression were found when the first 21 codons of the native sequence were deleted and the Trp immediately following the resulting N-terminal Met was changed to Ala (GCT).

Purification and characterization of the human liver cytochromes P-450 involved in debrisoquine 4-hydroxylation and phenacetin O-deethylation, two prototypes for genetic polymorphism in oxidative drug metabolism.

Relative expression of cytochrome P450 isoenzymes in human liver and association with the metabolism of drugs and xenobiotics.

Comparisons with a panel of drugs, carcinogens and model P450 substrates demonstrate and confirm that the correlations obtained in this manner represent a powerful approach towards the assignment of the metabolism of substrates by specific human P450 isoenzymes.

Role of phospholipids in reconstituted cytochrome P450 3A form and mechanism of their activation of catalytic activity.

Study of proteolytic digestion and chemical cross-linking in systems I and II showed that a P450 3A form needed disaggregation of cytochrome P-450 and/or the reductase, not the formation of an aggregated complex necessary for the catalytic activity of other cyto chrome P- 450s.

The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes.

Analysis of IIA proteins in human liver microsomes, using antibody against rat IIA2, revealed two proteins of 49 and 50 kDa, which appeared to correlate with human microsomal coumarin 7-hydroxylase activity, and a more striking correlation was found between IIA mRNA and enzyme activity.

Characterization of human lung microsomal cytochrome P-450 1A1 and its role in the oxidation of chemical carcinogens.

This work clearly shows that human lung microsomes contain at least two major P- 450 enzymes; human P-450 1A1 is present in lungs and can actually catalyze the activation of environmental procarcinogens, including polycyclic aromatic hydrocarbons.

Catalytic activities of human liver cytochrome P-450 IIIA4 expressed in Saccharomyces cerevisiae.

The results of these studies with a defined protein clearly demonstrate the ability of P-450 IIIA4 to catalyze regio- and stereoselective oxidations with a diverse group of substrates, and this enzyme appears to be one of the most versatile catalysts in the P- 450 family.

Human P450PCN1: sequence, chromosome localization, and direct evidence through cDNA expression that P450PCN1 is nifedipine oxidase.

The results suggest that a human P450 related to rat P450PCN1 is the major form of P450 catalyzing nifedipine oxidation, and this P450 is the primary enzyme associated with metabolism and inactivation of this important drug.

Changes in the amount of cytochrome P450s in rat hepatic microsomes with starvation.