Extramicrosomal drug metabolism

Drug metabolizing enzymes which are not located in the microsomes such as oxidoreductases are reviewed. It has been reported that a cytoplasmic NAD+-dependent dehydrogenase could be involved in the dehydrogenation of secondary or primary alcohols, and that peroxidases, located in all extranuclear cell-fractions, are able to oxidize certain drugs. Among the conjugating enzymes, mainly the glucuronidases and 0-Methyltransferases have been reported to be localised in the microsomes. Sulfatation, mercapturic acid formation and acetylation seem to occur in the supernatant of animal liver cells. Binding to glycine has been found in the mitochondria. Examples of combined action of microsomes and other cell fractions are presented. Esterases are found in the microsomes and cytoplasmic fraction of animal cells and also in the extracellular fluid (blood-plasma). They are more stable than monooxygenases whose activity depends on the intact microsomal structure and are therefore readily accessible in human biological material. Metabolic problems involving human esterases can often easily be solved by in vitro experiments. Results concerning the biochemical degradation of propanidid, mefrusid, acetyl salicylic acid and an acetyl salicylic acid ester are reported.