al., 1996). Although the liver is the major site of glucuronidation in the living organism,

several other tissues have been shown to express UGTs. The small intestine appears to be

an equally important site of glucuronidation, particularly for ingested xenobiotics. In

addition, expression of some UGT isoforms is tissue-specific (Table 2-1).

 The nine family 1 UGT isoforms (UGT1) are all encoded by one gene that has

multiple unique exons located upstream of four common exons on human chromosome

2q37 (Figure 2-3). The isoforms are generated by differential splicing of one unique first

exon (which encodes two-thirds of the lumenal domain, starting from the N-terminus,

288 amino acids long) to the four common exons (exons 2-5, which encode the remainder

of the lumenal domain, the transmembrane domain and the cytosolic tail, 246 amino

acids long). Due to this unusual gene structure and splicing mechanism, the UGT1

isoforms have variable amino-terminal halves and identical carboxyl-terminal halves.

While the first exon determines substrate specificity, the common exons specify the

interaction with UDPGA (Ritter et al., 1992; Gong et al., 2001). Thus, the major bilirubin

UGT (UGTIAl) of humans, rats and other species is encoded by exon 1 and the adjacent

4 common exons. The phenol UGT (UGTIA6) is encoded by exon 6 and the 4 common

exons.

 The human UGT2 gene family includes three members of the UGT2A subfamily

and twelve members of the UGT2B subfamily (Mackenzie et al., 2005). The UGT2

proteins are encoded by separate genes consisting of six exons located on human

chromosome 4ql3. The region of the protein encoded by exons 1 and 2 is equivalent to

that encoded by the unique exons 1 of the UGT1 isoforms, and the subsequent

intron/exon boundaries are in corresponding positions in both gene families. Similar to