SULFATION AND SULFOTRANSFERASES .5. THE IMPORTANCE OF 3'-PHOSPHOADENOSINE 5'-PHOSPHOSULFATE (PAPS) IN THE REGULATION OF SULFATION

Sulfation is the transfer of a sulfate group from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to a substrate that is catalyzed by a family of sulfotransferase enzymes. Many different endogenous and xenobiotic molecules are substrates for the sulfotransferases; sulfation affects many different physiological processes, including: I) deactivation and bioactivation of xenobiotics, 2) inactivation of hormones and catecho lamines, 3) structure and function of macromolecules, and 4) eliminati on of end products of catabolism. PAPS is the obligate cosubstrate tha t is synthesized in tissues to make available an ''activated form'' of sulfate for the sulfation reaction. PAPS participation in the reactio n is dependent on its availability, which in turn is dependent on its synthesis, degradation, and ultimately its utilization in the sulfatio n reaction itself. PAPS synthesis is dependent on the availability of sulfate and on the activity of the two enzymes of its synthesis, ATP-s ulfurylase and APS-kinase. Although the kinetic properties of these tw o enzymes are well described, their in vivo regulation is not fully un derstood. Sulfation is a high-affinity, low-capacity enzymatic process in which the entire liver content of PAPS can be consumed in less tha n 2 min. ATP-sulfurylase and APS-kinase can rapidly synthesize additio nal PAPS. The low capacity of sulfation in rats is due to the Limited availability of sulfate, whereas in mice the sulfotransferases appear to limit sulfation capacity. Sulfation rates are not readily enhanced, but they can be decreased. 2,6-Dichloro-4-nitrophenol inhibits phenol sulfotransferases, but not hydroxysteroid-sulfotransferases. However, the sulfation of phenols and hydroxysteroids can be decreased by facto rs that decrease sulfate availability such as a low-sulfate diet, othe r xenobiotics that are sulfated, and molybdate, which inhibits sulfate intestinal absorption, renal reabsorption, and sulfate incorporation into PAPS.