PMID: 2526Aug 1, 1975

Recent studies on cytochrome P-450-linked functions in isolated rat liver cells

Forensic Science
S OrreniusR Grundin

Abstract

In rat liver cells isolated by perfusion in the perfusion in the presence of collagenase, the major portion of cytochrome P-450 is present in the oxidized, nonsubstrate-bound, low spin state. Drug addition to a suspension of liver cells results in the rapid formation of the cytochrome P-450 (Fe3+)-substrate complex which in turn is followed by the appearance of other species with different spectral characteristics before steady state drug monooxygenation is achieved. Cytochrome P-450-linked metabolism of various tested drugs and carcinogenic polycyclic hydrocarbons by isolated rat liver cells is as fast, or faster, as with rat liver microsomes supplemented with a NADPH generating system. Both experimental models respond similarily to phenobarbital or 3-methylcholanthrene pretreatment of the animals and to various of the wellknown inhibitors of drug metabolism. Except with liver cells isolated from fasted, phenobarbital-treated rats, generation of cytosolic NADPH seems sufficient to support optimal drug metabolism even in the absence of added substrates of intermediary metabolism. In isolated liver cells oxidized drug metabolites undergo subsequent metabolic conversion, most often to form the corresponding glucuronides and sulph...Continue Reading

References

Mar 1, 1975·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·R A LubetG L Whitson
Jul 15, 1974·European Journal of Biochemistry·P MoldéusS Orrenius
Mar 1, 1971·Archives of Biochemistry and Biophysics·A Hildebrandt, R W Estabrook
Dec 10, 1973·Biochemical and Biophysical Research Communications·P MoldéusS Orrenius
Jul 10, 1974·Biochemical and Biophysical Research Communications·C von BahrS Orrenius

Citations

Jul 1, 1976·Agents and Actions·A Aitio
May 1, 1983·Acta Pharmacologica Et Toxicologica·J A HolmeE Dybing

Related Concepts

Ethanol
Metazoa
Cytochrome P-450 Oxygenase
Glucuronic Acids
Liver
Methylcholanthrene
Microsomes, Liver
NADP
Luminal
Uridine Diphosphate Glucuronic Acid

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