STEREOCHEMICAL HETEROGENEITY OF HEPATIC UDP-GLUCURONOSYLTRANSFERASE ACTIVITY IN RAT-LIVER MICROSOMES

Rat liver UDP glucuronosyltransferase activities may be divided into at least 2 groups with differential responses towards substrates. The chemical basis which may distinguish the 2 groups was studied. Glucuronidation of 24 substrates in liver-microsomes of Sprague-Dawley rats pretreated with 3-methylcholanthrene or phenobarbital was studied. The conjugation of 11 substrates was stimulated most strongly by 3-methylcholanthrene and that of the others, by phenobarbital. The estimated thickness of the molecule in their most likely conformation was < 4 .ANG. for molecules of the 1st group and > 4 .ANG. for the 2nd. The thickness or the bulkiness of the molecules is important. For phenol substituted in the position 2, a steric effect or intramolecular interactions may change the substrate''s classification within the 2 groups. It was noticed that phenobarbital stimulated more than 3-methylcholanthrene the glucuronidation of the corresponding hydroxylated metabolite.