Document Detail

Studies on the interactions of chiral secondary alcohols with rat hydroxysteroid sulfotransferase STa.
MedLine Citation:
PMID:  9351908     Owner:  NLM     Status:  MEDLINE    
Hydroxysteroid (alcohol) sulfotransferase STa catalyzes the 3'-phosphoadenosine 5'-phosphosulfate-dependent O-sulfonation of a diverse array of alcohols including neutral hydroxysteroids. Many of the secondary alcohols that interact with this sulfotransferase are the metabolic products 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 benzylic 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, the effect of stereochemistry on the catalytic efficiency of STa was small (less than 2-fold in favor of (R)-(+)-enantiomers). However, as the number of carbons in the alpha-alkyl chain increased, the stereoselectivity 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 with a 3-fold difference in catalytic efficiency. STa showed absolute stereospecificity in the sulfation of the enantiomers of 1-phenyl-1-cyclohexylmethanol; (R)-(+)-1-phenyl-1-cyclohexylmethanol was a substrate for STa, while the (S)-(-)-enantiomer was a competitive inhibitor of the enzyme. Although a lower degree of stereoselectivity was observed with the 3-hydroxyl-containing steroids, androsterone and epiandrosterone, results with these substrates were also consistent with the conclusion that the stereochemistry of secondary alcohols is an important factor in the catalytic efficiency of STa.
E Banoglu; M W Duffel
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  25     ISSN:  0090-9556     ISO Abbreviation:  Drug Metab. Dispos.     Publication Date:  1997 Nov 
Date Detail:
Created Date:  1998-02-09     Completed Date:  1998-02-09     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1304-10     Citation Subset:  IM    
Division of Medicinal and Natural Products Chemistry, College of Pharmacy, The University of Iowa.
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MeSH Terms
Alcohols / chemical synthesis,  chemistry*,  metabolism
Androsterone / metabolism
Benzyl Alcohols / chemical synthesis,  chemistry
Chemistry, Physical
Esters / chemical synthesis,  chemistry
Physicochemical Phenomena
Rats, Sprague-Dawley
Substrate Specificity
Sulfotransferases / antagonists & inhibitors,  chemistry*,  metabolism
Grant Support
Reg. No./Substance:
0/Alcohols; 0/Benzyl Alcohols; 0/Esters; 53-41-8/Androsterone; EC 2.8.2.-/Sulfotransferases; EC sulfotransferase

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