| pubmed-article:19420132 | pubmed:abstractText | N-Sulfoconjugation is a common metabolic pathway of amine compounds in vivo. In the present study, we 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 of the substrates examined with apparent K(m) values comparable to those mediated by hSULT2A1. The K(m) 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 humans. | lld:pubmed |
