[Multiplicity of sulfotransferases]

Area of Science:

• Biochemistry
• Enzymology
• Pharmacology

Context:

• Sulfation is a critical metabolic pathway for numerous endogenous compounds and xenobiotics, including drugs and carcinogens.
• Sulfation reactions are catalyzed by sulfotransferase (ST) enzymes found in cellular cytosols.
• The multiplicity and regulation of ST enzymes are complex and vary across species and tissues.

Purpose:

• To investigate the characteristics and regulation of rat and mouse sulfotransferase (ST) isoenzymes.
• To identify selective inhibitors of specific STs, such as tertiary amines for rat hepatic hydroxysteroid ST (HS-ST).
• To elucidate the structural determinants of substrate specificity and enzyme activity in STs through mutagenesis and chimera studies.

Summary:

• Tertiary amines selectively inhibit rat hepatic HS-ST.
• Developmental and zonal distribution patterns suggest complex regulatory mechanisms for rat liver HS-ST and phenol ST (P-ST).
• Site-directed mutagenesis and chimera studies on rat HS-ST cDNAs (ST-40 and ST-20) highlight the C-terminal region's importance for substrate specificity and multiple regions for enzyme activity.
• These rat HS-ST cDNAs map to chromosomal region 1q21.3-->q22.1.
• Mouse olfactory P-ST shares 94% amino acid identity with rat ST1C1 and is localized in olfactory sustentacular cells.

Impact:

• Provides insights into the substrate specificity and regulatory mechanisms of sulfotransferase enzymes.
• Identifies potential inhibitors for specific STs, relevant for drug metabolism and toxicology studies.
• Characterizes the genetic mapping and structural features of STs, contributing to our understanding of enzyme function and evolution.