STUDIES ON THE INTERACTIONS OF CHIRAL SECONDARY ALCOHOLS WITH RAT HYDROXYSTEROID SULFOTRANSFERASE STA

Hydroxysteroid (alcohol) sulfotransferase STa catalyzes the 3'-phospho adenosine 5'-phosphosulfate-dependent O-sulfonation of a diverse array of alcohols including neutral hydroxysteroids. Many of the secondary alcohols that interact with this sulfotransferase arcs the metabolic p roducts of stereoselective oxidation or reduction reactions. The role that the stereochemistry of secondary alcohol substrates plays in the catalytic efficiency Of STa was investigated with a series of chiral b enzylic alcohols and the enantiomeric 3-hydroxyl-containing steroids, androsterone and epiandrosterone, In the case of (R)-(+)- and (S)-(-)- enantiomers of 2-methyl-1-phenyl-1-propanol and 1-phenyl-1-butanol, th e effect of stereochemistry on the catalytic efficiency of STa was sma ll (less than 2-fold in favor of (R)-(+)-enantiomers). However, as the number of carbons in the alpha-alkyl chain increased, the stereoselec tivity for the sulfation of enantiomers increased as well. The (R)-(+) -enantiomers of 1-phenyl-1-pentanol, 1-phenyl-1-hexanol, and 1-phenyl- 1-heptanol were preferred as substrates over the (S)-(-)enantiomers wi th a 3-fold difference in catalytic efficiency. STa showed absolute st ereospecificity in the sulfation of the enantiomers of 1-phenyl-1-cycl ohexylmethanol; (R)-(+)-1-phenyl-1-cyclohexylmethanol was a substrate for STa, while the (S)-(-)-enantiomer was a competitive inhibitor of t he enzyme. Although a lower degree of stereoselectivity was observed w ith the 3-hydroxyl-containing steroids, androsterone and epiandrostero ne, results with these substrates were also consistent with the conclu sion that the stereochemistry of secondary alcohols is an important fa ctor in the catalytic efficiency of STa.