Sulfotransferases

Abstract

The sulfotransferases (SULTs) are a family of phase II enzymes that catalyze the transfer of a sulfonate group (‐SO 3− ) from the cofactor 3′‐phosphoadenosine‐5′‐phosphosulfate (PAPS) to an acceptor molecule or substrate. Since these enzymes can conjugate with a wide variety of xenobiotics and endogenous substrates, they function not only as drug‐metabolizing enzymes but also modulators of physiological activities through conjugations of endogenous molecules such as steroids, catecholamines, and thyroid hormones. This chapter aims to provide drug metabolism scientists with an introductory overview on various aspects of SULTs along with challenges and complications associated with SULT‐mediated biotransformations, particularly encountered during the drug discovery and development process. In recent years, commercially available hepatocyte preparations and recombinant SULT enzymes facilitate the determination of SULT involvement for compounds of interest. However, significant challenges do remain. For example, when conducting reaction‐phenotyping experiments for SULT‐catalyzed conjugations, there is currently a lack of well‐characterized isoform‐specific probe substrates and inhibitors, in addition to a lack of well‐established in vitro incubation conditions. Kinetic experiments, too, often require careful interpretation, as profound substrate inhibition is rather common for sulfation reactions. From the toxicology stand‐point, sulfation may pose liability concerns due to the potential formation of reactive electron‐deficient metabolite species. It is recommended that investigators should take the time to explore and understand the properties of SULT‐mediated conjugations and their implications.

Theoretical Study on Storage and Release of Firefly Luciferin

“…Therefore, the phosphate group on 3′‐phosphate‐binding loop of PAPS and PAP are likely to remain dianion state in the current luciferin sulfotransferase. The phosphate diester of 5′‐phosphate (phosphosulfate)‐binding loop in PAPS and PAP would be anionic basing on previous report (42), and the sulfuryl group with a pK a about 1 (43) in PAPS would also be ionized because the physical condition of firefly is near‐neutral (pH=7.4) (44). For convenience, we labeled the ionized state of PAP and PAPS as d ‐ PAP and d ‐ PAPS , respectively (see Figs.…”