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D Y Cooper

Publications and source records attributed to D Y Cooper.

At least 37 records · Page 2Linked to original sources
PubMed1977

Reductive titration of cytochrome P-450 in rat liver microsomes.

Microsomal cytochromes b5 and P-450 of rat liver have been titrated with standardized sodium dithionite solution with a newly developed titrating apparatus that allows spectrophotometric monitoring of the reduction process while strictly O2-free conditions are maintained throughout the procedure. Cytochrome b5 and other electron acceptors in the microsomal preparation were saturated with reducing equivalents prior to addition of carbon monoxide to the system. Continued titration in the presence of CO revealed that 1 electron equivalent was required for the formation of P-450(Fe2+)-CO. These results are in agreement with previous findings of 1 electron equivalence for cytochrome P-450 of adrenocortical mitochondria and P-450CAM.

Anaerobiosis↗
PubMed1977

Inhibition by CO of hepatic benzo[a]pyrene hydroxylation and its reversal by monochromatic light.

Inhibition by CO of benzo[a]pyrene hydroxylation was studied in hepatic microsomes from rats pretreated with phenobarbital, 3-methylcholanthrene or 2,3,7,8-tetrachlorodibenzo-p-dioxin, from animals treated with vehicle (saline or corn oil, respectively), and in a reconstituted microsomal cytochrome P-448 system prepared from rats treated with 3-methylcholanthrene. In all preparations the hydroxylation was inhibited by CO, and this inhibition was most effectively reversed by irradiation with monochromatic light of 450 nm wavelength. These observations provide direct evidence that the oxygen-activating component of all the examined benzo[a]pyrene hydroxylase systems is a P-450-type heme protein. The only striking difference observed in these systems was the low CO sensitivity of the benzo[a]pyrene hydroxylase reaction in microsomes from animals treated with 3-methylcholanthrene or 2,3,7,8-tetrachlorodibenzo-p-dioxin. Half-maximal inhibition occurred at CO/O2 ratios of 9--12, rather than at 1--2, which is the usual range for P-450-linked mixed-function oxidase reactions. In contrast, the reconstituted benzo[a]pyrene hydroxylase system, with purified cytochrome P-448 from 3-methylcholanthrene-induced rats, exhibited a considerably higher sensitivity towards CO (CO/O2 ratio approximately 1), well within the range for mixed-function oxidase reactions. It is concluded that the observed diminished CO sensitivity of microsomal benzo[a]pyrene hydroxylase in 3-methylcholanthrene- or 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats results from alterations in the composition and/or structural organization of the microenvironment of cytochrome P-448 in the endoplasmic reticulum in response to the inducing action of polycyclic aromatic hydrocarbons and related agents, and is not related to changes in the heme protein P-448 per se. The detailed nature of these changes is the subject of ongoing studies.

Animals↗
PubMed1975

Comparison of the induction course, biophysical chemical interactions and photochemical action spectra of phenobarbital and 3-methylcholanthrene induce hepatic microsomal P-450.

A comparison has been made of the physical and chemical properties of hepatic microsomal P-450 and associated enzyme systems from rats treated with phenobarbital or with 3-methylcholanthrene and other polycyclic aryl hydrocarbons. The results of these studies, though preliminary in nature, indicate clearly that the aryl-induced mixed-function oxidase systems differ significantly from the PB-induced ones in time course of induction, spectral properties, hyroxylase and demethylase activities, CO-inhibition of these reactions and light-reversal of the inhibition. The results support and extend the findings of other investigators regarding the differential biophysical and biochemical properties of aryl-induced systems and provide an experimental design for studying these properties in greater depth at the maximum of aryl induction.

Aniline Compounds↗