人类UDP-葡糖醛酰转移酶的基因多样性与胃肠道的调节
[引自Mol Pharmacol 2001 Mar;59(3):405-414]
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.
