Enzymatic characterization and interspecies difference of phenol sulfotransferases, ST1A forms

Cytosolic sulfotransferases, which mediate activation and detoxification of both endogenous and exogenous compounds, consist of at least five differen t gene families (ST1 to ST5) in mammals. Several cDNAs corresponding to ST1 A forms have been reported, but their functional properties are not well ch aracterized. In addition, only a single form of ST1A sulfotransferase has b een reported in each experimental animal species despite the expressions of plural forms in humans. Therefore, enzymatic properties of human ST1A3, ST 1A5, rat ST1A1, mouse St1a4, and newly isolated rabbit ST1A8 have been char acterized and compared by use of their recombinant proteins to clarify the functional difference between human and experimental animal ST1A forms. Fro m the results using more than 25 phenolic chemicals, all the experimental a nimal ST1A forms showed substrate specificities similar to human ST1A3 rath er than ST1A5. They showed high affinities toward p-nitrophenol and 6-hydro xymelatonin as found in human ST1A3. These forms also showed high activitie s toward umbelliferone and naringenin, but very low activities toward catec holamines, representative substrates of human ST1A5. Hepatic contents of ex perimental animal ST1A forms varied (66-250 pmol/mg of cytosolic protein) b ut showed the same order as observed with human ST1A3 (120 pmol/mg). Hepati c content of human ST1A5 was about 19-fold less than that of ST1A3. Therefo re, ST1A forms identified in experimental animal species correspond to huma n ST1A3 functionally. For chemicals such as troglitazone and 2-amino-4'-hyd roxy-1-methyl-6- phenylimidazo[4,5-b] pyridine, clear species differences w ere detected among the ST1A forms examined.