Tissue distribution of drug-metabolizing enzymes in humans

Abstract

Abstract1. The activities of the ethoxycoumarin O-deethylase (ECOD), epoxide hydrolase (EH), UDP-glucuronyl transferase (GT), glutathione S-transferase (GST), acetyl transferase (AT) and sulphotransferase (ST) were measured in 6 liver, 8 lung, 8 kidney, 8 intestinal mucosa and 22 urinary bladder mucosa specimens from human subjects. EH and GT were studied with styrene oxide and 1-naphthol, respectively, as substrates, GST, AT and ST were studied with benzo(a)pyrene-4,5-oxide, p-aminobenzoic acid and 2-naphthol, respectively.2. The enzyme activities were detectable at significant rates in liver, lungs, kidneys and gut. In urinary bladder, EH, GT, GST and ST only were detectable. The liver catalyzed the various reactions at higher rates than did other tissues.3. Of the extrahepatic tissues, the intestinal mucosa contained the highest activities of AT (50% of liver) and ST (30% of liver), whereas kidneys contained the highest activity of GT (50% of liver) and GST (80% of liver). GST was the enzyme with the widest tissue distribution.