| Title | Selective role of SULT2A1 in the N-sulfoconjugation of quinolone drugs in human. | | Author(s) | Senggunprai L, Yoshinari K, Yamazoe Y | | Institution | Tohoku University. | | Source | Drug Metab Dispos 2009 May 6. | | Abstract | N-Sulfoconjugation is a common metabolic pathway of amine compounds in vivo. In the present study, we have investigated the N-sulfation of quinolones and other amine drugs (ciprofloxacin, moxifloxacin, garenoxacin, desipramine and metoclopramide) to assess the contribution of specific human cytosolic sulfotransferases (SULTs) to the reactions using purified recombinant enzymes and human liver cytosols (HLCs). Among the enzymes examined, human (h) SULT2A1 exhibited N-sulfoconjugation activities toward all drugs tested, whereas the other five different forms (hSULT1A1, hSULT1A3, hSULT1B1, hSULT1C2 and hSULT1E1) showed no detectable activities except hSULT1A1 for garenoxacin sulfation. The N-sulfoconjugating activity of hSULT2A1 was highest toward moxifloxacin (6.3 +/- 0.1 nmol/min/mg protein) at the substrate concentration of 100 microM. Kinetic analyses demonstrated that HLC-mediated N-sulfations were monophasic for all the substrates examined with apparent Km values comparable to those mediated by hSULT2A1. The Km values for N-sulfation mediated by hSULT2A1 were as follows: 1.08 +/- 0.03 mM for ciprofloxacin, 0.53 +/- 0.01 mM for moxifloxacin, 0.19 +/- 0.01 mM for garenoxacin, 0.054 +/- 0.001 mM for desipramine, and 2.32 +/- 0.12 mM for metoclopramide. The sulfating activities of HLCs toward the amines were well correlated with those for O-sulfation of dehydroepiandrosterone, a hSULT2A1 probe substrate. Taken together, the present results unequivocally demonstrate that hSULT2A1 is responsible for the N-sulfation of quinolones and possibly other therapeutic drugs in human. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19420132 |
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