Interaction of drugs, steroids and fatty acids with liver-microsomal cytochrome P-450.

@article{Kupfer1970InteractionOD,
  title={Interaction of drugs, steroids and fatty acids with liver-microsomal cytochrome P-450.},
  author={David Kupfer and Sten Orrenius},
  journal={European journal of biochemistry},
  year={1970},
  volume={14 2},
  pages={
          317-22
        }
}
The interaction of various substrates with the cytochrome P-450 containing monooxygenase system of rat liver microsomes has been studied. Testosterone, triamcinolone acetonide (TrA) and laurate were found to interfere with the type I spectral changes produced by the addition of hexobarbital and ethylmorphine to suspensions of microsomes suggesting that these substrates bind to a common cytochrome P-450 species. Substrates producing a type I spectral change with liver microsomes, such as… 
Molecular aspects of drug metabolism.
  • S. Orrenius
  • Biology, Chemistry
    Acta pharmacologica et toxicologica
  • 1971
TLDR
It is suggested that the competitive inhibition that various substrates exert on each other's hydroxylation is due to a competition for binding to a common cytochrome P-450 species in the liver microsomes.
Effects of pesticides and related compounds on steroid metabolism and function.
  • D. Kupfer
  • Biology
    CRC critical reviews in toxicology
  • 1975
The studies reviewed were selected to describe those investigations that could provide mechanistic-biochemical interpretations for the effects of pesticides on steroid-mediated biological functions.
Uptake, metabolism and excretion of desmethylimipramine and its metabolites in the isolated perfused rat liver.
The isolated perfused rat liver was used in order to study the metabolism of the tricyclic antidepressant drug, desmethylimipramine (DMI), which is metabolized by oxidation and subsequent
Properties of purified kidney microsomal NADPH-cytochrome c reductase.
Mechanism-based in vivo inactivation of lauric acid hydroxylases.
TLDR
Fatty acid analogues in which the carboxylic acid group is replaced by a sulfate moiety, or in which two methyl groups are placed vicinal to the car boxylic Acid group, have been found to inactivate lauric acid hydroxylases in vitro and in vivo without causing time-dependent inhibition of ethoxycoumarin O-deethylation or N-methyl-p-chloroaniline N-demethylation.
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References

SHOWING 1-10 OF 20 REFERENCES
Studies on the rate of reduction of hepatic microsomal cytochrome P-450 by reduced nicotinamide adenine dinucleotide phosphate: effect of drug substrates.
TLDR
The data suggest that the complexes formed between cytochrome P-450 and type I compounds are more readily reduced by NADPH than is the endogenous hemoprotein.
Inhibition of drug metabolism. V. Inhibition of drug metabolism by steroids.
In a study employing hepatic microsomes from rats, estradiol-17β, testosterone, androsterone, progesterone, and hydrocortisone inhibited competitively the oxidation of ethylmorphine and hexobarbital.
Relation between biological activity of hydrocortisone analogues and their rates of inactivation by rat liver enzyme systems.
TLDR
It is stated that C-20 and δ4-3 ketone Reduction of hydrocortisone, as well as ketone reduction of a number of other steroids, occurs in a combined microsome-supernatant fraction of rat liver.
Pharmacological implications of microsomal enzyme induction.
  • A. Conney
  • Biology, Medicine
    Pharmacological reviews
  • 1967
TLDR
It is of considerable interest that certain inducers of liver microsomal enzymes have recently been used therapeutically for the treatment of hyperbilirubinemia in jaundiced children and for thetreatment of Cushing's syndrome.
SIMILARITIES BETWEEN OXIDATIVE DRUG-METABOLIZING ENZYMES AND STEROID HYDROXYLASES IN LIVER MICROSOMES.
TLDR
Liver microsomal enzymes oxidatively metabolize steroids and foreign compounds in the presence of TPNH and oxygen to compounds which are more polar than the substrate suggest that steroid hormones are normally occurring substrates for oxidative drug-metabolizing enzymes in liver microsomes.
Photochemical Action Spectrum of the Terminal Oxidase of Mixed Function Oxidase Systems
TLDR
The agreement between photochemical action spectrum and spectrophotometric difference spectrum supports the conclusion that the CO-binding pigment is the terminal oxidase of mixed function oxidase systems of mammals.
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