Studies of mammalian glucoside conjugation

Abstract

The mammalian glucoside-conjugation pathway was studied by using p-nitrophenol as the model substrate and mouse liver microsomal preparations as the source of enzyme. The microsomal preparations supplemented with UDP-glucose glucosylated p-nitrophenol; p-nitrophenyl glucoside was identified by chromatography in six solvent systems. The unsolubilized glucosyltransferase of fresh microsomal preparations did not follow the usual Michaelis–Menten kinetics and was easily inhibited by many steroids. All the steroids tested inhibited glucosylation of p-nitrophenol to a greater degree than glucuronidation of p-nitrophenol when assayed in the same microsomal preparations. The steroids inhibited glucosylation with the following decreasing effectiveness: pregnan-3α-ol-20β-one (3α-hydroxypregnan-20-β-one)>oestradiol-17β 3-methyl ether>oestradiol-17β>oestriol>pregnane-3α,20β-diol>oestrone. Pregnan-3α-ol-20β-one, pregnane-3α,20β-diol and oestrone had negligible effect on glucuronidation.