E. Banoglu et Mw. Duffel, STUDIES ON THE INTERACTIONS OF CHIRAL SECONDARY ALCOHOLS WITH RAT HYDROXYSTEROID SULFOTRANSFERASE STA, Drug metabolism and disposition, 25(11), 1997, pp. 1304-1310
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.