UDP-Glucuronosyltransferases (UGTs)

 The primary sequence of human UGTs ranges from 529 to 534 amino acids in

length (Tukey and Strassburg 2000). These 50-56 kDa proteins reside in the endoplasmic

reticulum, whereby the amino terminus and around 95% of the subsequent residues are

located in the lumen. A 17-amino acid-long transmembrane segment connects the

lumenal part of the enzyme with the short (19-24 residues) carboxyl-terminus located in

the cytosol (Figure 2-2). The active enzyme probably consists of dimers, linked together

at the C-terminus (Meech and Mackenzie 1997). The existence of tetramers for the

formation of the diglucuronide of B[a]P-3,6-diphenol has been suggested (Gschaidmeier

and Bock 1994).

 ++
 COO. Cytosol

 ER
 III membrane

 ER lumen

 NH3+
 Ag lycone
 UDPGA






Figure 2-2. Proposed structure of UGT, based on amino acid sequence

 Based on evolutionary divergence, mammalian UGTs have been classified into four

distinct families (Mackenzie et al., 2005): family 1, which includes bilirubin, thyroxine

and phenol UGTs; family 2, which includes steroid UGTs; family 3, which includes

UGTs whose substrate specificity is, as yet, unknown (Mackenzie et al., 1997); family 8,

represented by UGT8Al which utilizes UDP-galactose as the sugar donor (Ichikawa et