110-92-9Relevant articles and documents
Influence of substrate structure on the catalytic efficiency of hydroxysteroid sulfotransferase STa in the sulfation of alcohols
Chen, Guangping,Banoglu, Erden,Duffel, Michael W.
, p. 67 - 74 (2007/10/03)
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.
ENZYMIC SYNTHESIS OF STEROID SULFATES XVI. SPECIFICITY AND REGULATION OF HUMAN ADRENAL HYDROXYSTEROID SULFOTRANSFERASE
Adams, J. B.,McDonald, D.
, p. 575 - 586 (2007/10/02)
Pure hydroxysteroid sulfotransferase (EG 2.8.2.2) of human adrenal glands possesses a wide substrate specificity towards steroids.This wide specificity has now been found to extend to simple alcohols; normal aliphatic alcohols from C3 onwards acting as substrates with C9 showing the highest rate.Increased rate was accompanied by a decrease in Km.In marked contrast to the sulfurylation of steroids such as dehydroepiandrosterone, which exhibit wave-like kinetics, the kinetics with simple alcohols were of the normal Michaelis-Menten type.By means of enzyme antibody and enzyme stability studies evidence was provided that one and the same enzyme was responsible for sulfurylation of hydroxyls on the 3- and 17-positions of steroids and simple alcohols.The data lend support to previous evidence that the enzyme controls the secretion of dehydroepiandrosterone sulfate via steroid-specific binding sites, enabling self-regulation in response to ACTH action.
