Functional and immunochemical comparison of hepatic UDP-glucuronosyltransferases in a piscine and a mammalian species

Douglas J. Clarke, Brian Burchell, Stephen G. George

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

1. 1. The aglycone specificity of hepatic microsomal glucuronidation was compared under uniform conditions in a fish, Pleuronectes platessa and a mammal, Rattus norvegicys, representative of the most primitive and advanced vertebrate classes. 2. 2. Both species exhibited comparable UDP-glucuronosyltransferase (UDPGT) activity towards planar phenolic substrates (1-napthol, 4-nitrophenol); however, plaice activity towards bulky non-planar substrates such as (-)-morphine was either 200-fold lower, or for arylacetic acid (RS-2-phenylpropionic acid) and an aryloxyacetic acid (clofibric acid) non-detectable. 3. 3. Conjugation of the endogenous substrates, bilirubin and steroids were 4- to 40-fold lower in the plaice than in the rat. Whilst both species formed diglucuronides of the asymmetrical bilirubin IXα, they displayed a reciprocal preference for the initial esterification, conjugation of the C-8 side chain predominating in the rat and of C-12 in the fish. 4. 4. Immunoblot analysis using two polyclonal antisera preparations raised against rat UDPGTs demonstrated the presence of multiple weakly cross-reacting polypeptides in fish microsomes indicative of multiple isoforms and conservation of common structural motifs over more than 350 million years since evolutionary divergence of the mammals.

Original languageEnglish
Pages (from-to)425-432
Number of pages8
JournalComparative Biochemistry and Physiology -- Part B: Biochemistry and
Volume102
Issue number2
DOIs
Publication statusPublished - 1 Jun 1992
Externally publishedYes

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