Relationship between paracetamol binding to and its oxidation by two cytochromes P-450 isozymes--a proton nuclear magnetic resonance and spectrophotometric study.
From the hepatic cytochrome P-450 isozymes b and c isolated from rats treated with phenobarbital and 3-methylcholanthrene respectively, only cytochrome P-450c was found to be active in the oxidation of paracetamol, in the presence of glutathione ultimately leading to the formation of the 3-glutathionyl conjugate. Paracetamol interacted with both cytochrome P-450b and c, as shown by difference spectrophotometry. Cytochrome P-450b was found to have a higher affinity for paracetamol than cytochrome P-450c and demonstrated a type I spectral change, whereas in the case of cytochrome P-450c a reverse type I spectral change was observed. Proton n.m.r. longitudinal relaxation rate measurements revealed that in the case of cytochrome P-450c, paracetamol was orientated with its phenolic hydroxyl group in closest proximity to the central haem iron ion. In the case of cytochrome P-450b, the acetylamino group of paracetamol most closely approached the haem iron ion.
D000082:Acetaminophen / Q000378:metabolism*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010084:Oxidation-Reduction; D011485:Protein Binding; D051381:Rats; D013057:Spectrum Analysis
D007527:Isoenzymes; D000082:Acetaminophen; D003577:Cytochrome P-450 Enzyme System