Figure 3.

Human sulfation pathways are complex. The various parts of human sulfation pathways are schematically depicted. Several sulfate transporters are responsible for cellular sulfate uptake (reviewed in Refs. 59 and 62), followed by the two-step enzymatic sulfate activation by bifunctional PAPS synthases. PAPS is then either used directly by cytoplasmic and nuclear sulfotransferases or shuttled to the Golgi apparatus to serve a multitude of Golgi-residing carbohydrate and protein sulfotransferases. In contrast to the nonsulfated biomolecules, sulfated xenobiotics or steroids need designated organic anion transporters to enter or exit cells. Many different sulfatases exist to cleave sulfate esters again. The otherwise toxic, sulfation by-product PAP needs to be removed by dedicated phosphatases (reviewed in Ref. 65). In this review, we focus on sulfate activation, steroid sulfation, and desulfation as well as the transport of steroid sulfates via organic anion transporters. For all other steps, the reader may refer to the reviews given above.