Stereoselective sulphate conjugation of fenoterol by human phenolsulphotra nsferases

Abstract

1. The objective of this study was to determine (1) the molecular site(s) of sulphoconjugati on of fenoterol; (2) the human phenolsulphotra nsferase (PST) isoform(s) involved; and (3) the stereochemistry of the enzymatic reaction. 2. Using the human Hep G2 cell line, hplc isolation and FAB/ms/ms, it was determined that fenoterol is sulphated both in the 4′-hydroxyphenylposition and in one of the 3′,5′-dihydroxyphenylpositions. 3. Recombinant human M-PST preferentially sulphated the 4′-hydroxyphenyl position. In contrast, recombinant P-PST exclusively sulphated the 3′,5′-hydroxyphenyl position. 4. The M-PST-catalysed sulphation of the 4′-hydroxyphenyl position was highly selective for the active RR-enantiomer, whereas the sulphation of the 3′,5′-dihydroxyphenyl position was slightly selective for the opposite SS-enantiomer. 5. The P-PST-catalysed sulphation of the 3′,5′-hydroxyphenyl position was selective for the inactive SS-enantiomer.