Journal article
Importance of peri -Interactions on the Stereospecificity of Rat Hydroxysteroid Sulfotransferase STa with 1-Arylethanols
Chemical research in toxicology, Vol.12(3), pp.278-285
03/01/1999
DOI: 10.1021/tx980219f
PMID: 10077491
Abstract
Sulfotransferase a (STa) is an isoform of hydroxysteroid (alcohol) sulfotransferase that catalyzes the formation of sulfuric acid esters from both endogenous and xenobiotic alcohols. Among its various functions in toxicology, STa is the major form of hepatic sulfotransferase in the rat that catalyzes the formation of genotoxic and carcinogenic sulfuric acid esters from hydroxymethyl polycyclic aromatic hydrocarbons. The goal of the present study was to elucidate fundamental quantitative relationships between substrate structure and catalytic activity of STa that would be applicable to these and other xenobiotics. We have modified previous procedures for purification of STa in order to obtain sufficient amounts of homogeneous enzyme for determination of k(cat)/K(m) values, a quantitative measure of catalytic efficiency. We determined the catalytic efficiency of STa with benzyl alcohol and eight benzylic alcohols that were substituted with n- alkyl groups (C(n)H(2n+1), where n = 1-8) in the para position, and the optimum value for k(cat)/K(m) in these reactions was obtained with n- pentylbenzyl alcohol. Correlations between logarithms of k(cat)/K(m) values and logarithms of partition coefficients revealed that hydrophobicity of the substrate was a major factor contributing to the catalytic efficiency of STa. Primary n-alkanols (C(n)H(2n+1)OH, where n = 3-16) exhibited an optimum k(cat)/K(m) for C9-C11 and a linear decrease in v(max) of the reaction for C3-C14; 15- and 16-carbon n-alkanols were not substrates for STa. These results indicated limits to the length of the extended carbon chain in substrates. Such limits may also apply to hydroxysteroids, since cholesterol was inactive as either substrate or inhibitor of STa. Furthermore, the importance of steric effects on the catalytic efficiency of STa was also evident with a series of linear, branched, and cyclic seven-carbon aliphatic alcohols. In conclusion, our results provide fundamental quantitative relationships between substrate structure and catalytic efficiency that yield insight into the specificity of STa for both endogenous and xenobiotic alcohols.
Details
- Title: Subtitle
- Importance of peri -Interactions on the Stereospecificity of Rat Hydroxysteroid Sulfotransferase STa with 1-Arylethanols
- Creators
- Erden Banoglu - University of IowaMichael W. Duffel - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Chemical research in toxicology, Vol.12(3), pp.278-285
- DOI
- 10.1021/tx980219f
- PMID
- 10077491
- ISSN
- 0893-228X
- eISSN
- 1520-5010
- Language
- English
- Date published
- 03/01/1999
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984303286602771
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