Monooxygenase activities of human liver, lung, and kidney microsomes - a study of 42 post mortem cases

The cytochrome P-450-dependent monooxygenase system was examined in microsomal fractions prepared from 42 post mortem human livers and 9 lungs and kidneys. Electron microscopy studies indicated that the human liver samples were relatively free of mitochondrial and plasma membrane contamination, but samples of kidney and lung were less pure. The microsomal fractions from all organs were judged to be relatively free of haemoglobin and methaemoglobin. The specific enzyme activities for several drug substrates for the monooxygenase, NADPH-cytochrome c reductase activity and the content of the microsomal cytochromes were measured. The values of the biochemical parameters studied were found to be quite variable and the values for the human liver were appreciably lower than those obtained with liver microsomes from laboratory rodents. The enzyme activities of the human kidney and lung microsomal fractions were 1-10% of those seen for human liver samples, except for NADPH-cytochrome c(P-450) reductase activity. In order to evaluate any post mortem changes in human liver, correlations between drug metabolism activities and either cytochrome P-450 or NADPH-cytochrome c (P-450) reductase content were examined. Strong correlations (r greater than 0.91) were seen only between aminopyrine or ethylmorphine demethylase activity and cytochrome P-450 content in samples obtained within 4 hours of death. Longer post mortem times gave poorer correlation between activity and cytochrome content. These studies document several conditions required in order to obtain human microsomal fractions representative of the activities in fresh, viable tissue.