Introduction: Changing view of sulfation and the cytosolic sulfotransferases

OUR UNDERSTANDING OF THE physiological roles of sulfation and the complexity of the sulfotransferase (ST)2 gene family that catalyzes these reactions has been rapidly increasing during the last decade. Because of its early association with the conjugation of drugs and xenobiotics, sulfation was generally considered to be a Phase II conjugation reaction in drug metabolism (1). This view has been changing asit becomes apparent that sulfation and the sulfotransferases have a variety of important functions in tissues. The transfer of a sulfonate group from the donor compound 3’ -phosphoadenosine 5’-phosphosulfate (PAPS) to an acceptor compound is catalyzed by a large family of enzymes called sulfotransferases. The major acceptor groups are aromatic or aliphatic hydroxyls whose conjugation gives rise to a sulfate moiety. However, the STs are also capable of conjugating other structural groups, including primary amines, N-oxides, and hydroxyl amines. The name “sulfation” was derived from early studies that identified phenolic sulfate esters in the urine of humans and animals treated with phenols. Not until the identification of PAPS as the donor of the “active sulfate” group (2) did it become apparent that a sulfonate group (SO3) was being transferred in the reactions rather than a sulfate group. Although it would be more appropriate to call these sulfonation reactions, the term sulfation is still more widely used to describe them. Only within the last 10 years has the complexity of the ST gene family become evident. The ST family consists of both the membrane-associated enzymes, which are primarily localized in the trans-Golgi apparatus, and the cytosolic enzymes, which are more commonly associated with the sulfation of small drugs, steroids and thyroid hormones, and xenobiotics. The Golgi-associated STs are membrane-bound enzymes involved in the sulfation of glycosaminoglycans, glycoproteins, and tyrosines in pro-