MAJOR HYDROXYSTEROID SULFOTRANSFERASE STA IN RAT-LIVER CYTOSOL MAY CONSIST OF 2 MICROHETEROGENEOUS SUBUNITS

The possible existence of two microheterogeneous subunits, designated ST-40P and ST-41P, of hydroxysteroid sulfotransferases in female Sprag ue-Dawley rat liver cytosol was demonstrated by cloning and sequencing of cDNAs, both isolated from two rat liver cDNA libraries. These subu nits consisted of an equal number of amino acid residues with only one amino acid substitution. ST-40P and ST41P expressed as homodimers fro m the ST-40 and ST-41 cDNAs in Escherichia coil had enzyme activities toward all of the examined 20 hydroxysteroids, 13 bile acids, and the carcinogen 5-hydroxymethylchrysene (5-HCR), with formation of the reac tive metabolite 5-HCR sulfate, at rates very similar to those by STa, the major hydroxysteroid sulfotransferase in rat liver cytosol. This s trongly suggested that they are essential components of STa. The prese nt study carried out by using the recombinant enzymes provides the fir st direct evidence for the identity of sulfotransferases catalysing th e sulfation of hydroxysteroids and bile acids and proposes that the cu rrent nomenclature system used for distinguishing hydroxysteroid sulfo transferases from bile acid sulfotransferases should be improved.