conjugate is pharmacologically active, as in the case of morphine-6-glucuronide

(Yoshimura et al., 1973) and minoxidil sulfate (Buhl et al., 1990).

 The moieties attached to the xenobiotic in the case of sulfonation and

glucuronidation are a sulfonate group (pKa 2) or glucuronic acid (pKa 4-5). The co-

substrates which supply these highly polar species are, respectively, 3'-phosphoadenosyl-

5'-phosphosulfate (PAPS) and uridine 5' -diphosphoglucuronic acid (UDPGA) (Figure 2-

1). The mechanism of both reactions, which occurs as a ternary complex, is a SN2

reaction, the deprotonated acceptor group of the substrate attacking the sulfur in the

phosphosulfate bond of PAPS, or the C1 of the pyranose ring to which UDP is attached in

an ot-glycosidic bond in the case of UDPGA. The resulting conjugates are then released.

PAP and UDP also leave the enzyme's active site and are subsequently regenerated.

 There may be competition for the same acceptor group, especially for phenols.

Other acceptor groups that can be conjugated by both processes include alcohols,

aromatic amines and thiols. Glucuronidation is also active on other functional groups,

including carboxylic acids, hydroxylamines, aliphatic amines, sulfonamides and the C2 Of

1 ,3 -di carb onyl compounds. SULTs are generally high-affinity, low-capacity

biotransformation enzymes that operate effectively at low substrate concentrations. Thus,

typical Knas for the sulfonation of xenobiotic substrates are usually significantly lower

than Knas for the same substrates undergoing biotransformation by the low-affinity, high-

capacity UGTs. For example, kinetic parameters for the sulfonation and glucuronidation

of the antimicrobial agent triclosan in human liver are Km values of 8.5 and 107 C1M and

Vmax of 96 and 739 pmol/min/mg protein respectively (Wang et al., 2004).