Stereoselective sulphate conjugation of fenoterol by human phenolsulphotransferases.
1. The objective of this study was to determine (1) the molecular site(s) of sulphoconjugation of fenoterol; (2) the human phenolsulphotransferase (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'-hydroxyphenyl position and in one of the 3',5'-dihydroxyphenyl positions. 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.
Wilson
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AA
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston 29425, USA.
Wang
J
J
Koch
P
P
Walle
T
T
D001993:Bronchodilator Agents / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular; D002851:Chromatography, High Pressure Liquid; D005280:Fenoterol / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008113:Liver Neoplasms; D011994:Recombinant Proteins / Q000378:metabolism; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013237:Stereoisomerism; D013379:Substrate Specificity; D013431:Sulfates / Q000378:metabolism*; D015238:Sulfotransferases / Q000378:metabolism*; D013462:Sulfur Radioisotopes; D015149:Tocolytic Agents / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D001993:Bronchodilator Agents; D007527:Isoenzymes; D011994:Recombinant Proteins; D013431:Sulfates; D013462:Sulfur Radioisotopes; D015149:Tocolytic Agents; D005280:Fenoterol; D015238:Sulfotransferases