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Vol. 59, Issue 3, 405-414, March 2001
Departments of Pharmacology and Chemistry & Biochemistry,
University of California, San Diego, La Jolla, California (R.H.T.); and
Department of Gastroenterology and Hepatology, Hannover Medical School,
Hannover, Germany (C.P.S.)
The metabolism of ingested foods and orally administered drugs occurs
in the hepato-gastrointestinal tract. This process is facilitated by
several supergene families that catalyze oxidative metabolism as well
as conjugation of the small molecular weight substances that enter the
systemic circulation through resorption in the gastrointestinal tract.
The catalytic action carried out by one of several conjugation
reactions leads to the eventual elimination of the resultant
metabolites from the cell. As early as 1959 (R. T. Williams,
Detoxification Mechanisms) it was suggested that the
detoxification of most agents is efficiently performed by the phase II
conjugation reactions, because the addition of bulky, water-soluble
groups to the target substrates facilitates the partitioning of these
metabolites from the lipid into the aqueous compartments of the cell.
The combined efforts of the phase II reactions provides remarkable
redundancy in a biological system that seems to be designed to assure
that many endogenously generated catabolic products as well as
exogenous agents introduced through the surface tissues of the
digestive tracts are efficiently removed through excretion to the bile
or urine. In this review, we focus on recent findings that highlight
the genetic multiplicity and regulatory patterns of the phase II
superfamily UDP-glucuronosyltransferases (UGTs). Although much is known
regarding the number of UGTs that make up the UGT1 and
UGT2 gene families, as demonstrated after the
characterization of expressed cDNAs, examples are also presented in
which information obtained from the human genome project will aid in
the final characterization of the genetic multiplicity. In addition,
tools have now been developed and examples presented to identify the
expression patterns of the UGTs in human tissues, paying particular
attention to expression patterns of these genes in the
hepato-gastrointestinal tract.
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