Multiplicity of sulfotransferases

Abstract

Sulfation is an important conjugation reaction in the metabolism of a diversity of xenobiotics and endogenous compounds such as drugs, food additives, carcinogens, steroids and neurotransmitters. Sulfate conjugation is catalyzed by various kinds of sulfotransferase (ST) such as hydroxysteroid ST (HS-ST), phenol ST (P-ST) and estrogen ST (E-ST) present in cytosols. Our laboratory has been studying the multiplicity of rat and mouse STs. We found that tertiary amines such as triethylamine selectively inhibited rat hepatic HS-ST. Developmental changes and zonal distributions of rat liver HS-ST and P-ST isoenzymes provided evidence for their complex regulatory mechanisms. Studies on site-directed mutagenesis and chimeras of rat HS-ST cDNAs, ST-40 and ST-20, revealed the importance of the C-terminal region for the substrate specificity and involvement of multiple regions for the enzyme activities. These two cDNAs have been mapped to the same chromosomal region 1q21.3-->q22.1 by fluorescence in situ hybridization. Mouse olfactory P-ST was present in the cytoplasm of olfactory sustentacular cells and its cloning study revealed that it is 94% identical with rat ST1C1 in amino acid sequences.