The Formation of N-Glucuronides Catalyzed by Purified Hepatic 17β-Hydroxysteroid and 3α-Hydroxysteroid UDP-Glucuronyltransferases

  • Mitchell D. Green
  • Yacoub Irshaid
  • Thomas R. Tephly
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 197)

Abstract

Conjugation of many endogenous and exogenous chemicals with glucuronic acid, catalyzed by UDP-glucuronyltransferases (EC 2.4.1.17), is an important step in their detoxification and elimination from the body. We have previously reported on the purification of three different UDP-glucuronyltransferases (UDPGTs) from hepatic microsomes of female Sprague-Dawley rats1. A 17β-hydroxysteroid UDPGT catalyzes the glucuronidation of the 17β-hydroxy position of steroids, such as testosterone and 17β-estradiol, and xenobiotics such as p-nitrophenol and 1-naphthol. A 3α-hydroxysteroid UDPGT has been purified which is specific for the glucuronidation of the 3α-position of steroids and bile acids2,3. A 3-methylcholanthreneinducible form of p-nitrophenol UDPGT catalyzes the conjugation of various xenobiotic substrates, such as p-nitrophenol, 4-methylumbelliferone and 1-naphthol, with glucuronic acid1.

Keywords

Testosterone Androgen Biphenyl Phosphatidylcholine Phenobarbital 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    C. N. Falany and T. R. Tephly, Separation, purification and characterization of three isoenzymes of UDP-glucuronyltransferase from rat liver microsomes, Arch.Biochem.Biophys. 227: 248 (1983).CrossRefGoogle Scholar
  2. 2.
    R. B. Kirkpatrick, C. N. Falany and T. R. Tephly, Glucuronidation of bile acids by rat liver 3–0H androgen UDP-glucuronyltransferase, J. Biol. Chem. 259: 6176 (1984).PubMedGoogle Scholar
  3. 3.
    C. N. Falany, R. B. Kirkpatrick and T. R. Tephly, Comparison of rat and rabbit liver UDP-glucuronyltransferase activities, in: “Advances in Glucuronide Conjugation,” S. Matern, K. W. Bock and W. Gerok, eds., MTP Press, Lancaster (1985).Google Scholar
  4. 4.
    E. Boyland, D. Manson and S. F. D. Orr, The biochemistry of aromatic amines. 2. The conversion of arylamines into arylsulphamic acids and arylamine-N-glucosiduronic acids, Biochem. J. 65: 417 (1957).Google Scholar
  5. 5.
    I. M. Arias, Ethereal and N-linked glucuronide formation by normal and Gunn rats in vitro and in vivo, Biochem. Biophys. Res. Commun. 6: 81 (1961).CrossRefGoogle Scholar
  6. 6.
    F. F. Kadlubar, L. E. Unruh, T. J. Flammang, D. Sparks, R. K. Mitchum and G. J. Mulder, Alteration of urinary levels of the carcinogen, N-hydroxy-2-naphthylamine, and its N-glucuronide in the rat by control of urinary pH, inhibition of metabolic sulfation and changes in biliary excretion, Chem.. - Biol. Interact. 33: 129 (1981).PubMedCrossRefGoogle Scholar
  7. 7.
    R. H. Tukey, R. E. Billings and T. R. Tephly, Separation of oestrone UDP-glucuronyltransferase and p-nitrophenol UDP-glucuronyltransferase activities, Biochem. J. 171: 659 (1978).Google Scholar
  8. 8.
    W. Lilienblum and K. W. Bock, N-Glucuronide formation of carcinogenic aromatic amines in rat and human liver microsomes, Biochem. Pharmacol. 33:2041 (1984).Google Scholar
  9. 9.
    R. H. Tukey and T. R. Tephly, Purification and properties of rabbit liver estrone and p-nitrophenol UDP-glucuronyltransferases, Arch. Biochem. Biophys. 209: 565 (1981).Google Scholar
  10. 10.
    C. Y. Wang, K. Zukowski and M. S. Lee, Glucuronidation of carcinogenic arylamine metabolites by rat liver microsomes, Biochem. Pharmacol. 34: 837 (1985).PubMedCrossRefGoogle Scholar
  11. 11.
    M. Matsui, F. Nagai and S. Aoyagi, Strain differences in rat liver UDP-glucuronyltransferase activity towards androsterone, Biochem. J. 179: 483 (1979).Google Scholar
  12. 12.
    M. Matsui and M. Hakozaki, Discontinuous variation in hepatic uridine diphosphate glucuronyltransferase toward androsterone in Wistar rats. A regulatory factor for in vivo metabolism of androsterone, Biochem. Pharmacol. 28: 411 (1979).Google Scholar
  13. 13.
    M. D. Green, C. N. Falany, R. B. Kirkpatrick and T. R. Tephly, Strain differences in purified rat hepatic 3α-hydroxysteroid UDP-glucuronosyltransferase, Biochem. J. In press (1985).Google Scholar
  14. 14.
    G. M. Bonser, D. B. Clayson, J. W. Jull and L. N. Pyrah, The carcinogenic properties of 2-amino-l-naphthol hydrochloride and its parent amine 2-naphthylamine, Br. J. Cancer 6: 412 (1952).PubMedCrossRefGoogle Scholar
  15. 15.
    D. B. Clayson and R. C. Garner, in: “Chemical Carcinogens,” C.E. Searle, ed., American Chemical Society, Washington, D.C. (1976).Google Scholar
  16. 16.
    R. M. Hicks, R. Wright and J. St. J. Wakefield, The induction of rat bladder cancer by 2-naphthylamine, Br. J. Cancer 46: 646 (1982).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Mitchell D. Green
    • 1
  • Yacoub Irshaid
    • 1
  • Thomas R. Tephly
    • 1
  1. 1.Toxicology Center Department of PharmacologyUniversity of IowaIowa CityUSA

Personalised recommendations