Lipophilicity of acceptor substrate as a factor in “late foetal” rat liver microsomal UDP-glucuronosyltransferase activity

Abstract

The UDP-glucuronosyltransferase activity towards phenolic compounds, as measured by initial velocity, has been directly related to lipophilicity of acceptor substrates, as obtained by measurement of octanol-buffer or octanol-water partition. The acceptor substrates examined include 17 compounds, all probably conjugated by the “late foetal” enzyme activity. Rat liver microsomal enzyme activity towards five acceptor substrates of the “late foetal” enzyme was examined under different activation conditions. A statistically significant, partition-dependent increase in activity was observed when the effects of ageing or Triton X-100 treatment were studied. With n-pentane, phospholipase C or UDP- N-acetylglucosamine, although the enzyme activity depended on the partition coefficient of the acceptor substrate, activity towards each substrate was enhanced by a similar amount. Mild trypsin treatment (which did not itself activate the enzyme) or ageing converted the n-pentane dependent general activation into a partition related form by reducing the activity of the enzyme towards the less lipophilic substrates. Removal of phospholipid from the membrane by n-pentane or hydrolysis by phospholipase C resulted in the partition independent activation. Protein release, which by itself did not activate the enzyme, was also required for a partition-dependent effect. As enzyme activity towards the five substrates was induced by 3-methylcholanthrene, but not by phenobarbital, the “late foetal” enzyme was being studied. The induced enzyme activity appeared similar to the non-induced activity.