Characterization of recombinant human liver thermolabile phenol sulfotransferase with minoxidil as the substrate.
Minoxidil, a potent antihypertensive agent and hair growth stimulator, is metabolized by phenol sulfotransferase to its activated form, minoxidil sulfate. The thermostable form of phenol sulfotransferase was reported to be the enzyme that catalyzed the reaction. Our previous findings with partially purified human platelet preparations indicated that the thermolabile form of phenol sulfotransferase also catalyzed the sulfation of minoxidil. To confirm and to characterize precisely the activity of thermolabile phenol sulfotransferase toward minoxidil, we investigated the ability of the enzyme expressed from a human liver cDNA clone to sulfate minoxidil during testing of thermal stability and of inhibition by 2,6-dichloro-4-nitrophenol and NaCl. The cDNA encoded thermolabile phenol sulfotransferase activity assayed with minoxidil behaved in the same fashion as the activity measured with dopamine, a finding that confirmed that this enzyme activity sulfated minoxidil. Thus, thermolabile phenol sulfotransferase must be taken into account with the thermostable enzyme when estimating the human tissue sulfotransferase contribution to minoxidil sulfation.
Kudlacek
P E
PE
Section of Endocrinology and Metabolism, Department of Veterans Affairs Medical Center, Omaha, NE 68105, USA.
Clemens
D L
DL
Anderson
R J
RJ
D000818:Animals; D015239:Arylsulfotransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D004795:Enzyme Stability; D006358:Hot Temperature; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008914:Minoxidil / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity
D011994:Recombinant Proteins; D008914:Minoxidil; D015239:Arylsulfotransferase