Glucuronidation in the rat intestinal wall. Comparison of isolated mucosal cells, latent microsomes and activated microsomes

Biochem Pharmacol. 1983 Mar 1;32(5):895-900. doi: 10.1016/0006-2952(83)90594-4.

Abstract

Glucuronidation and sulphation of 1-naphthol and 7-hydroxycoumarin was studied in isolated rat intestinal epithelial cells and in microsomes prepared from these cells. In the isolated cells formation of 1-naphthol sulphate could not be detected. Sulphate conjugates of 7-hydroxycoumarin constitute a minor portion of total conjugates formed. Maximum glucuronidation rates for 1-naphthol and 7-hydroxycoumarin do not differ significantly from each other (approximately 12.5 nmoles/min X g intestine). The intestinal microsomal UDP-glucuronosyltransferase, prepared from isolated cells, could be activated in vitro by Triton X-100 and MgCl2. Activation increased both Kappm and Vmax for 1-naphthol; Kappm for UDP-glucuronic acid was decreased by activation with MgCl2 but increased again by further addition of Triton X-100. In fully activated microsomes Kappm for 1 naphthol was 69.7 +/- 13.9 microM and Vmax was 70.0 +/- 3.9 nmoles/min X mg microsomal protein; Kappm for UDP-glucuronic acid was 0.67 +/- 0.06 mM. The glucuronidation rate (expressed as nmoles/min X g intestine) in microsomes is substantially higher than in isolated cells. It appears that glucuronidation in intact cells is limited by factors other than the extracellular substrate concn. Both cellular uptake of the substrate and availability of UDP-glucuronic acid can play a significant role. It is concluded that isolated mucosal cells are more suitable for predicting intestinal first-pass metabolism of phenolic xenobiotics than intestinal microsomes, because cellular substrate uptake and cosubstrate availability appear to be important determinants of the maximum glucuronidation rate.

MeSH terms

  • Animals
  • Biological Availability
  • Enzyme Activation / drug effects
  • Epithelium / metabolism
  • Glucuronates / metabolism*
  • In Vitro Techniques
  • Intestinal Mucosa / metabolism*
  • Male
  • Microsomes / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Subcellular Fractions / metabolism
  • Sulfates / metabolism

Substances

  • Glucuronates
  • Sulfates