Cytochrome P-450 — Its Function in the Oxidative Metabolism of Drugs

  • Ronald W. Estabrook
Part of the Handbook of Experimental Pharmacology / Handbuch der experimentellen Pharmakologie book series (HEP, volume 28 / 2)


The oxidative transformation of a large variety of compounds of pharmacological interest is known to occur primarily in the liver. The participation in these reactions of an enzyme complex associated with the disrupted endoplasmic reticulum (microsomal fraction) of liver was established in the mid-1950’s by the group at the National Institutes of Health under the direction of B.B. Brodie (Brodie, 1955; Cooper and Brodie, 1955). Indeed, this laboratory has served as the major source of investigators and ideas for the work which has led to our present understanding of the multitude of parameters modifying drug metabolism. Biochemical studies on drug metabolism gained their initial impetus from the studies of R.T. Williams and his collaborators (1959), who identified many of the products formed in the body and characterized the major pathways of detoxification. Parallel to the studies by BRODIE and his group were a number of other investigations directly related to the biochemical mechanism of such oxidative reactions. Studies of the metabolic pathways for steroids (Samuels, 1961), the use of oxygen-18 to assess the role of molecular oxygen (Hayano et al., 1955; Mason, 1957; Hayaishi, 1962), the spectrophotometric study of microsomal pigments (Klingenberg, 1958), and the detailed investigation by pharmacologists of “drug tolerance” (Conney et al., 1956, 1960; Burns et al., 1955; Remmer, 1959), all came to the forefront at about the same time. Examination of each of these facets of the problem added to our present understanding of the mechanism of drug hydroxylation reactions, reactions that are now classified as mixed function oxidation (Mason, 1957) or monooxygenase (Hayaishi, 1962) type reactions.


Liver Microsome Oxidative Metabolism Spectral Change Difference Spectrum Microsomal Fraction 
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© Springer-Verlag Berlin · Heidelberg 1971

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  • Ronald W. Estabrook

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