Characterisation and Regulation of UDP-Glucuronosyltransferases
Many drugs, xenobiotics and endogenous compounds are metabolised via common two stage pathway, which was designated as phase 1 (oxidative metabolism) and phase II (conjugation) by Williams (1). Glucuronidation reactions catalysed by the UDP-glucuronosyltransferases (UDPGTs) is arguably the major conjugation system of phase II metabolism. The metabolism of phenacetin, in the example illustrated below (Fig 1), proceeds via oxidative dealkylation to produce paracetamol, a reactive and potentially toxic metabolite. Paracetamol is then rapidly glucuronidated to form a harmless water soluble metabolite which is excreted via the kidneys and urine.
KeywordsDEAE Cellulose Lithocholic Acid Ammonium Sulphate Fractionation Glucuronidation Reaction Hepatic Endoplasmic Reticulum
Unable to display preview. Download preview PDF.
- 1.Williams, R.T. “Detoxication Mechanisms” 2nd Ed. Chapman & Hall, London 1959.Google Scholar
- 2.Dutton, G.J. “The Biosynthesis of Glucuronides in Glucuronic Acid”, G J Dutton, ed., Academic Press, New York, pp 185–299 (1966).Google Scholar
- 3.Dutton, G.J. “Glucuronidation of Drugs and Other Compounds”, CRC Press, Boca Raton, Florida (1980).Google Scholar
- 4.Dutton G.J. and Burchell, B. Newer aspects of glucuronidation Pros. Drug. Metab. 2: 1–70 (1977).Google Scholar
- 8.Burchell, B., Identification and purification of multiple forms of UDP-glucuronosyltransferase, Rev. Biochem. Toxic. 3: 1–39 (1981).Google Scholar
- 9.Burchell, B., Studies on the Purification of rat liver UDP-glucuronyltransferase Biochem. J. 161: 534–549 (1977).Google Scholar
- 17.Coughtrie, M.W.H., Burchell, B., Leakey, J.E.A. and Hume, R., The inadequacy of perinatal glucuronidation Molec. Pharmac. 34: 729–735 (1988).Google Scholar
- 18.Hallinan, T. and De Brito, A.E.R., Topology of endoplasmic reticular enzyme systems and its possible regulatory significance. in: “Hormone and Cell Regulation”, Vol 5, pp 73–95 J E Dumont and J. Nunez, eds., Elsevier, Amsterdam (1981).Google Scholar
- 22.Iyanagai, T., Haniv, M., Sagawa, K. Fujii-Kuriyama, Y., Watanabe, S., Shively, J.E. and Anan, K.F., Cloning and characterisation of a cDNA encoding 3-methylcholanthrene inducible rat mRNA for UDP-glucuronosyltransf erse, J Biol. Chem. 261: 15607–15614 (1986).Google Scholar