Elsevier

Biochemical Pharmacology

Volume 30, Issue 18, 15 September 1981, Pages 2569-2575
Biochemical Pharmacology

Research paper
Dose-dependent shifts in the sulfation and glucuronidation of phenolic compounds in the rat in vivo and in isolated hepatocytes: The role of saturation of phenolsulfotransferase

https://doi.org/10.1016/0006-2952(81)90584-0Get rights and content

Abstract

The role of enzyme-kinetic parameters of sulfotransferase and UDP-glucuronyltransferase in the balance between sulfation and glucuronidation of various phenolic substrates was studied in the rat in vivo after i.v. administration and in isolated hepatocytes. A pronounced shift from sulfation to glucuronidation was observed in vivo upon increasing the dose of two phenols, harmol and phenol. Similar shifts were found when these compounds were incubated with isolated hepatocytes. However, the shift from sulfation to glucuronidation was small when 4-chlorophenol, or absent when 4-t-butylphenol were given in vivo. Such shifts were also absent when 4-chlorophenol and 4-t-butylphenol were incubated at increasing concentrations with isolated hepatocytes. The in vivo results with the various phenols were very similar to the conjugation patterns found in isolated hepatocytes. This suggests that these conjugations in hepatocytes are regulated by similar factors as in the intact animal.

In isolated hepatocytes at most 16 per cent of the available pool of inorganic sulfate was consumed during the incubation. Since Cheng and Levy have shown [J. biol. Chem.255, 2637 (1980)] that uptake of inorganic sulfate by hepatocytes is very rapid, the present results suggest that the limitation of sulfation of harmol and phenol at increasing dose was caused by saturation of the overall sulfation process by the acceptor substrate, rather than by depletion of inorganic sulfate.

References (27)

  • J.G. Weitering et al.

    Biochem. Pharmac.

    (1979)
  • P. Eyer et al.

    Biochem. Pharmac.

    (1978)
  • P. Moldéus

    Biochem. Pharmac.

    (1978)
  • P. Wiebkin et al.

    Biochem. Pharmac.

    (1978)
  • G.J. Mulder et al.

    Biochem. Pharmac.

    (1974)
  • M.K. Cassidy et al.

    Biochem. Pharmac.

    (1980)
  • R.J. Vonk et al.

    Biochem. Pharmac.

    (1978)
  • S. Cheng et al.

    J. biol. Chem.

    (1980)
  • R.T. Williams
  • I.D. Capel et al.

    Xenobiotica

    (1972)
  • R.T. Williams

    Biochem. J.

    (1938)
  • R. Mehta et al.

    Xenobiotica

    (1978)
  • H.G. Sammons et al.

    Biochem. J.

    (1941)
  • Cited by (0)

    View full text