Determination of drug metabolizing enzymes in needle biopsies of human liver.

A micromethod is described for determination of the cytochrome P-450 content, demethylation rate of aminopyrine and p-nitroanisole, the activities of NADPH-cytochrome-c-reductase, pseudocholinesterase and glucose-6-phosphatase in homogenates of the small amount of human liver (about 20 mg) obtained by needle biopsy. 1 g of human liver contains 32-38 mg microsomal protein, much less than that present in rat liver (50-60 mg/g liver). The cytochrome P-450 content in normals was 10.8±2.6 nmoles/g liver wet weight (mean±1 S.D.). In severe hepatitis and cirrhosis the cytochrome P-450 content fell to 50% of the control value, whereas mild and moderate hepatitis did not produce any change. Similarly, only in seriously damaged livers were the demethylationrates of both substrates lowered. The activity of the NADPH-cytochrome-c-reductase was 1.88±0.51 micromoles/g liver × min and was not impaired even by severe liver damage. The activities of glucose-6-phosphatase and pseudocholinesterase also fell only in severe liver disease. [ABSTRACT FROM AUTHOR]