Sulfation of benzylic alcohols catalyzed by aryl sulfotransferase IV.
Aryl sulfotransferase (AST) IV catalyzes the 3'-phosphoadenosine 5'-phosphosulfate-dependent sulfation of a variety of benzylic alcohols. Several molecular characteristics of benzylic alcohols were investigated for their ability to influence the catalytic efficiency of a homogeneous preparation of rat hepatic AST IV. The results of these studies indicated that lipophilicity of the benzylic alcohol was a major factor in determining catalytic efficiency, as represented by the values of kcat/Km. Furthermore, this effect was primarily mediated by a decrease in the apparent Km as a function of increasing lipophilicity of the molecules. This effect of lipophilicity was documented by a linear correlation between the apparent Km values of the benzylic alcohols and the logarithms of their octanol/water partition coefficients. In contrast to previously observed effects of para substituents on phenols, electronic effects of substituents on the phenyl ring had no effect on the catalytic efficiency of the enzyme with benzylic alcohols. In a further difference between phenol and benzylic alcohol substrates for AST IV, 2-naphthol exhibited pronounced substrate inhibition at pH 7.0, whereas the analogous benzylic alcohol, 2-naphthalenemethanol, did not. Stereochemistry at the benzylic carbon also had an effect on the catalytic efficiency of the AST IV; kcat/Km values for S-(-)-1-phenylethanol were approximately 3-fold higher than for R-(+)-1-phenylethanol.
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Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City 52242.
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D000818:Animals; D015239:Arylsulfotransferase; D001592:Benzyl Alcohols / Q000378:metabolism*; D001593:Benzyl Compounds / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009281:Naphthalenes / Q000378:metabolism; D009284:Naphthols / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013379:Substrate Specificity; D013431:Sulfates / Q000378:metabolism*; D013466:Sulfurtransferases / Q000378:metabolism*
D001592:Benzyl Alcohols; D001593:Benzyl Compounds; D009281:Naphthalenes; D009284:Naphthols; D013431:Sulfates; C055629:2-naphthalenemethanol; D013466:Sulfurtransferases; D015239:Arylsulfotransferase; C028405:2-naphthol