Sulfonation is generally a detoxification pathway whereby the conjugated
product has greater water solubility and is therefore excreted more readily
from the body. However, several chemicals have been shown to form
mutagenic and carcinogenic reactive electrophiles upon sulfonation (Glatt,
2000). Additionally, it is the sulfonated forms of minoxidil and cholecystokinin
that elicit biologic activity (Weinshilboum et al., 1997).
3.2.1 Cellular Location and Tissue Expression
Cytosolic SULTs exist as homodimers or heterodimers in solution. Cytosolic
SULTs are responsible for the conjugation of endogenous substrates such as
steroids, bile acids, and neurotransmitters, as well as several xenobiotics.
Membranebound SULTs are present in the Golgi apparatus of cells, and
catalyze sulfonation and posttranslational modification of peptides, proteins,
lipids, and glycosaminoglycans. Sulfonation activity is found to be the highest
in the liver and small intestine, although other organs also express the SULTs.
Endogenous steroids are sulfonated in most mammalian tissues, with high
activity in the adrenal tissue, kidney, and brain.
3.2.2 The SULT Superfamily of Cytosolic Enzymes
The cytosolic SULTs form a large superfamily of genes. Members of this
superfamily are assigned families and subfamilies based on amino acid
homology (Blanchard et al., 2004). Thus, members of a family share at least
FIGURE 3.6 Common SULT substrates. Arrows indicate site of sulfonation for each
substrate.
64 CONJUGATIVE METABOLISM OF DRUGS