Linked Life Data

19420132

Source:http://linkedlifedata.com/resource/pubmed/id/19420132

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2009-7-20
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Arylsulfotransferase, http://linkedlifedata.com/resource/pubmed/chemical/Dehydroepiandrosterone, http://linkedlifedata.com/resource/pubmed/chemical/Quinolones, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins, http://linkedlifedata.com/resource/pubmed/chemical/SULT1A1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/SULT1C2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Sulfates, http://linkedlifedata.com/resource/pubmed/chemical/Sulfotransferases, http://linkedlifedata.com/resource/pubmed/chemical/alcohol sulfotransferase, http://linkedlifedata.com/resource/pubmed/chemical/estrone sulfotransferase, http://linkedlifedata.com/resource/pubmed/chemical/iodothyronine sulfotransferase, http://linkedlifedata.com/resource/pubmed/chemical/monoamine-sulfating phenol...
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1521-009X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1711-7
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Selective role of sulfotransferase 2A1 (SULT2A1) in the N-sulfoconjugation of quinolone drugs in humans.
pubmed:affiliation
Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aramaki-aoba, Aoba-ku, Sendai, Miyagi, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't