Modification of microsomal lipid peroxidation and drug metabolism by cytoplasmic copper.

NADPH-dependent microsomal lipid peroxidation (LPO) can be influenced by addition of cytoplasmic supernatant as was demonstrated by Gram and Fouts (Arch. Biochem. Biophys. 114, 331-335, 1966). Small quantities of hepatocellular supernatant stimulate LPO, higher concentrations are inhibitory. These opposed effects depend on the relative concentrations of copper and iron, either as ions or protein-bound. A mathematical model is given to predict the formation of malondialdehyde as indicator of LPO in dependence of these metals. The copper-containing superoxide dismutase was shown to be without effect on LPO, whereas coeruloplasmin was inhibitory. Inhibition of LPO by copper ions or by TRIS buffer increased the linearity of microsomal ethylmorphine demethylase.