Methylation of captopril in human liver, kidney and intestine.

1. The methylation of captopril was studied in the microsomal fraction from 20 human liver, 12 kidney, and 14 intestinal mucosa specimens. 2. The hepatic methyltransferase activity (mean +/- SD) was 477 +/- 204 pmol/min per mg. Renal and intestinal methyltransferase activities were 3 and 8 times lower, respectively, than hepatic activity. 3. The kinetics of methyltransferase with captopril as substrate were studied in four specimens of liver, kidney and intestine. The maximum velocities of reaction (mean +/- SD; pmol/min per mg) were 697 +/- 219 (liver), 456 +/- 120 (renal cortex), 264 +/- 77 (renal medulla) and 101 +/- 28 (ileum mucosa). Km values (mean +/- SD; mM) were 5.2 +/- 2.3 (liver) 4.3 +/- 1.7 (renal cortex) 4.1 +/- 1.5 (renal medulla) and 5.3 +/- 2.0 mM (ileum mucosa). Vmax is subjected to a marked tissue dependence whereas Km is similar in all tissues. 4. Liver is the primary site of captopril methylation whereas the intestine plays only a minor role. Kidney may contribute substantially to the hepatic methylation of captopril.